Homogeneous Catalysts Types Reactions and Applications

CHEMICAL ENGINEERING METHODS AND TECHNOLOGY
HOMOGENEOUS CATALYSTS:
TYPES, REACTIONS AND APPLICATIONS
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CHEMICAL ENGINEERIN
NG METHODS
S AND TECHN
NOLOGY
HOMOG OUS CATALY

GENEO A YSTS:
TYPESS, REA
ACTION D APPL
NS AND LICATIIONS
ANDREW
W C. POE
EHLER
EDITOR
Nova Scien
nce Publisheers, Inc.
N York
New
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Homogeneous catalysts : types, reactions, and applications / editor, Andrew

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p. cm.
Includes index.
ISBN 978-1-61324-749-5 (eBook)
1. Catalysts. I. Poehler, Andrew C.
QD505.H647 2010
660'.2995--dc22
2010043903
Published by Nova Science Publishers, Inc. © New York

CONTENTS
Preface vii
Chapter 1 Metallic Nanoparticles Nanocomposites:
Their Catalytic Applications 1
Rocío Redón, N. G. García-Peña and F. Ramírez-Crescencio
Chapter 2 Recent Evolution of Oxidation Catalysis by Mo Complexes 43
Carla D. Nunes and Pedro D. Vaz
Chapter 3 Homogeneous Catalysts Based on Bis(imino)pyridine Complexes
of Iron, Cobalt, Vanadium and Chromium:
The Kinetic Peculiarities of Ethylene Polymerization 97
N.V. Semikolenova, A.A. Barabanov, L.G. Echevskaya,
M.A. Matsko and V.A. Zakharov
Chapter 4 Rational Design of Chiral Ruthenium Complexes
for Asymmetric Hydrogenations 127
Jiří Václavík, Petr Kačer and Libor Červený
Chapter 5 Supramolecular Gel Catalyst:
Bridging Homogeneous and Heterogeneous Catalysis 155
Jianyong Zhang and Stuart L. James
Chapter 6 Glycerol as a Sustainable Solvent for Homogeneous Catalysis 185
Adi Wolfson, Christina Dlugy and Dorith Tavor
Chapter 7 Homogeneous Catalysis in Carbonylative Coupling Reactions 205
Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage
Chapter 8 Synthesis, Characterization and Catalytic Stud of Oxovanadium
(IV) Complexes with Tetradentate Schiff Bases 233
A.P.A. Marques,, E.R. Dockal, Ieda Lucia Viana Rosa
and F.C. Skrobot
Chapter 9 Unique Design Tools for the Synthesis and Design of Dendrimers
as Supports for Recoverable Catalysts and Reagents
and their Applications in Asymmetric Synthesis 247
Ashraf A. El-Shehawy
vi Contents
Chapter 10 Recent Strategies in Phase Transfer Catalysis and its Application

in Organic Reactions 325
P.A.Vivekanand and Maw-Ling Wang
Chapter 11 Hexenoic Acids and their Derivatives – Preparation using Selective
Homogeneous Catalysts 371
Libor Červený and Eliška Leitmannová
Chapter 12 Homogeneous Catalyzed Succinoylation of Cellulose
in Ionic Liquids 387
C.F. Liu, A.P. Zhang, W.Y. Li, W. Lan and R.C. Sun
Chapter 13 Palladium Complexes of N-Heterocyclic Carbenes in Homogeneous
Catalysis and Biomedical Applications 403
Chandrakanta Dash and Prasenjit Ghosh
Chapter 14 Methods for Enhancing the Activity and Selectivity
of Homogeneous Catalysts in the Oxidation Processes 463
Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov
Index 499
PREFACE
In chemistry, homogeneous catalysis is a sequence of reactions that involve a catalyst in

the same phase as the reactants. Topics discussed in this book include the catalytic
applications of metallic nanoparticles nanocomposites; olefin oxidation chemistry based on
Mo catalysts; homogeneous catalysts based on Bis(imino) pyridine complexes of iron, cobalt,
vanadium, and chromium; Ru catalysts in asymmetric hydrogenation; supramolecular gel
catalysts; glycerol as a sustainable solvent for homogeneous catalysis; homogeneous catalysis
in carbonylative coupling reactions and methods for enhancing the activity and selectivity of
homogeneous catalysts in the oxidation process.
Chapter 1 – More than a simple review, this is a compilation of what has been done so far
in relation to metallic nanoparticle-polymer composites with applications in catalysis reported
up to now. The authors are going through all the transition metals from scandium to the noble
metals to the copper group. Also, they report that, basically, the noble or platinum group
metals are the metals commonly used as catalysts although some of the others have been
proven to work as catalysts on different reactions.
Chapter 2 – For 80% of all compounds produced in chemical and pharmaceutical
industry at least one catalytic step is essential during their synthesis. Catalysts speed up
chemical reactions but can be recovered unchanged at the end of the reaction. They can also
direct the reaction towards a specific product and allow reactions to be carried out at lower
temperatures and pressures with higher selectivity towards the desired product. This is a
principle that is pursued with increasing emphasis and dedication leading to far more specific
and cleaner processes.
Homogeneous catalysts, on the other hand are usually complexes, which consist of a
metal centre surrounded by a set of organic ligands. The latter impart solubility and stability
to the metal complex and can be used to tune the selectivity of a particular catalyst towards
the synthesis of a particular desirable product. By varying size, shape and electronic
properties of the ligands, the active site at which the substrate binds can be constrained in
such a way that only one of a large number of possible products can be produced. Oxidation
catalysis is a quite important transformation in both industrial and academic aspects. Within
this field, catalysts, ranging from a variety of available metal centered systems, which rely on
Mo are one of the most important.
Traditionally, oxidation catalysts are based on metal oxides, holding M=O moieties, with
the metal center lying in high oxidation state. A large number of important chemical reactions
are catalyzed by MoVI complexes. Inclusively, several industrial processes such as
viii Andrew C. Poehler
ammoxidation of propene to acrylonitrile, olefin epoxidation (ARCO and Halcon processes),

and olefin metathesis reactions are carried out over molybdenum catalysts. Furthermore, as
molybdenum is highly available to biological systems, the coordination chemistry of MoVI
has stimulated considerable interest in view of its biochemical relevance, and many MoVI
complexes have been studied as models of molybdoenzymes.
In recent years the development of new approaches to prepare new and stable catalyst has
turned to low oxidation state MoII organometallic complexes. These pre-catalysts proved to
be quite adequate to the purpose by being highly active and selective in the epoxidation of
olefins and in oxidation of other substrates. Additionally, such pre-catalyst complexes are
more stable towards air and moisture which allows easier handling.
This chapter lights up some recent advances on olefin oxidation chemistry based on Mo
catalysts with special focus on the development of new approaches to achieve active catalysts.
Chapter 3 – The family of highly active ethylene polymerization catalysts based on the
complexes of transition metals with bis(imino)pyridine ligands has been intensively studied in
the last ten years. In this study the authors summarize the known data and present new kinetic
results on the ethylene polymerization over homogeneous catalysts based on Fe(II), Co(II),
V(III) and Cr(III) bis(imino)pyridine complexes with close ligand framework (2,6-(2,4,6-
R3LMeCln, where R= H, Me, i-Pr, t-Bu, L=(C6H3N=CMe)2C5H3N, M= Fe(II), Co(II), V(III),
Cr(III), n=2,3).
The effects of the activator nature (different samples of methylalumoxane (MAO), or
aluminium trialkyls) and polymerization conditions on the activity of these complexes and the
resulted PE structure (molecular weight, molecular weight distribution, content of methyl and
vinyl groups) have been studied.
For the first time the number of active centers and propagation rate constant for ethylene
polymerization with Fe(II), Co(II), Cr(III) and V(III) bis(imino)pyridine complexes, activated
with MAO and Al(i-Bu)3, have been determined using method of polymerization inhibition
by radioactive carbon monoxide (14CO).
The experimental data obtained in comparable conditions have shown that the catalytic
properties of bis(imino)pyridine complexes ( polymerization activity, number of active
centers and propagation rate constant, copolymerization reactivity, composition of optimal
activator, formation of single site or multiple sites catalytic system, catalysts thermal stability
and PE structure) are mainly determined by transition metal center of complex. The size of
the substituents R in 2,6-positions of arene ring in the ligand L affects the number of active
centers and molecular weight of PE as well.
Chapter 4 – Thorough optimization of reaction conditions for maximum yield is the
essential prerequisite of every reaction conducted on an industrial scale. In the field of
asymmetric chemistry, an additional yield requirement arises, i.e. the stereoselectivity of the
reaction. The plethora of fine chemical products available on the world market indirectly
demands constant improvements in the production processes and literally dictates an
individual, made-to-measure solution for the best efficacy. The relentless expansion of the
product range thus demands rapid but reliable tools for finding the optimal reaction
conditions for a synthesis of the chiral product in question.
Naturally, there is no catalyst to suit all substrates. Much like enzymes, almost every
reaction requires at least a slightly modified catalyst or reaction conditions. Trial-and-error
syntheses and subsequent testing of all (at first sight) potentially effective catalysts are as
costly and time consuming as traditional combinatory methods, due to immense possibilities
Preface ix
of the catalyst and substrate structures. Many of the complexes prepared by these laborious
procedures finally prove ineffective when trying to utilize them in a stereoselectively
catalyzed reaction. Therefore, the objective is to synthesize only those truly offering the
desired behaviour. While only a few metal centres can be used effectively (namely Ru, Rh,
Os, Ir), the auxiliary ligands offer infinite solutions of key changes to the structure. The
rational design has become a well-known term to describe the process of fine-tuning the
ligand. Although this chapter focuses on Ru catalysts, Rh complexes are also mentioned,
owing to the high parallelism of these two coordination centres in the field of asymmetric
hydrogenation.
The term “rational design” comprises the practice of altering the molecular structures
aided by computational modelling. Bearing in mind the structure of the chiral product, an
experienced theoretical-organic chemist should be able to assemble a well-founded series of
ligands offering good possibilities of achieving the desired performance in a particular
situation. This process involves a competent rejection of structures with a significant potential
of failure with regards to enantioselectivity. Given the vast number of possibilities, such a
process would ideally be performed automatically, i.e. either by high-throughput
experimentation (HTE) techniques, which have been amply reviewed [1] and are not covered
within this chapter despite their rapid development in recent years, or through computational
chemistry. This preliminary virtual assay is often referred to as in silico screening. Recently,
high-capacity virtual ligand libraries have been created and analyzed, allowing a systematic
description of existing ligands and a subsequent prediction of the properties of analogues.
Computational methods on various levels of complexity are available, enabling us to refine
the search results by stepwise reduction of the number of potentially successful catalysts by
employing more sophisticated techniques.
Nevertheless, it ought to be noted that empirical findings still maintain an inimitable and
supreme role. Molecular modelling is doubtless a powerful tool but one needs to appreciate
that even models of the highest accuracy are still an approximation and will never yield 100%
match.
Nowadays, there are thousands of ligands used in asymmetric syntheses and millions of
further possibilities. Nonetheless, the reader is advised to note that this chapter concentrates
on those used in asymmetric hydrogenation. Ligands used for asymmetric hydroformylation,
hydrocyanation, reductive amination, allylic alkylation, hydrosilylation etc., are not covered.
Occasionally, however, some of these are mentioned as explanatory references that may be
applied to all ligands, including those for hydrogenation.
Chapter 5 – Supramolecular gels have received growing attention in recent years. They
represent a novel type of soft materials which may find application in various aspects.
Various organogels and metallogels offer rich possibilities for catalysis. Supramolecular gels
can be used in catalysis by incorporating a catalytically active unit as part of the gelator.
There are three strategies in literature: 1) catalysis by discrete gelators; 2) catalysis by
coordination polymer gelators; 3) catalysis by post-modified gels. Unique new catalytic
properties can arise from combining gels with catalytically active centres. Interestingly
supramolecular gels show enhanced activity compared with their homogeneous analogues in
a number of cases. They exhibit some combined advantages of homogeneous and
heterogeneous catalysis.
Chapter 6 – With its promising physical and chemical properties, glycerol can be used as
a sustainable solvent in many catalytic and non-catalytic organic reactions. Polar and non-
x Andrew C. Poehler
toxic, glycerol is a biodegradable, recyclable liquid that is manufactured from renewable

sources and that facilitates the dissolution of organic substrates, inorganic compounds, and
transition metal complexes. Glycerol also enabled easy isolation of the reaction product either
by extraction with glycerol immiscible solvents such as diethyl ether, ethyl acetate, and
supercritical carbon dioxide or through distillation. Using glycerol as a solvent also enabled
catalyst recycling, emulsion-like systems, and microwave-promoted reactions. Furthermore,
in many reactions, the use of glycerol as a solvent promoted improved activities and
selectivities of the reactants. In addition, in certain reactions such as the catalytic transfer-
hydrogenation of various unsaturated organic compounds and the transesterification of
alcohols, glycerol was used as both solvent and reactant.
Chapter 7 – Carbon monoxide is a ubiquitous molecule in organometallic chemistry and
an important feedstock in multiple catalytic processes both at the laboratory and industrial
levels. Palladium-catalyzed carbonylation reactions of alkenes/alkynes, aromatic halides with
different nucleophiles have undergone rapid development since the pioneering work of Reppe
and Heck, such that nowadays plethora of palladium catalysts and various synthetic protocols
are available for the synthesis of aliphatic and aromatic carboxylic acids as well as their
derivatives.
The carboxylic acid and its derivatives like amides, esters, thioamides etc. and ketones
prepared in this way are important intermediates in the manufacture of dyes, pharmaceuticals,
agrochemicals, and other industrial products. The term carbonylation covers a large number
of closely related reactions that all have in common that carbon monoxide is incorporated into
a substrate by the addition of CO to an aryl-, benzyl- or vinylpalladium complex in presence
of suitable nucleophiles.
Various carbonylation reactions like alkoxycarbonylation, phenoxycarbonylation,
aminocarbonylation, thiocarbonylation, carbonylative Suzuki coupling reaction, carbonylative
Sonogashira coupling reaction etc. have been explored using palladium as a catalyst of
choice.
Palladium along with variety of ligands has been widely employed as homogeneous
catalysts to affect carbonylation reactions. The scope of carbonylation reactions is also
extended for the synthesis of pharmaceuticals and their important intermediates using
carbonylation as the key step using homogeneous catalysis, which reveals that complex
synthetic processes can be accomplished under carbonylation conditions.
Herein, the authors summarize the recent developments in homogeneous catalysts and
selected organic applications in this area.
Chapter 8 – The synthesis, characterization and catalytic study of Oxovanadium (IV)
complexes and yours precursors Schiff bases [N,N’-bis(salicylidene)-1,2-phenylenediamine],
[N,N’-bis(salicylidene)-1,3-phenylenediamine] and [N,N’-bis(salicylidene)-1,3-
xylylenediamine] are reported. The Schiff base ligands were characterized by elemental
analysis, melting points, Fourier Transformed Infra-red spectroscopy, electronic spectroscopy
and 1H and 13C Nuclear Magnetic Resonance spectra. The oxovanadium (IV) complexes were
characterized by elemental analysis, melting points, Fourier Transformed Infra-red
spectroscopy and electronic spectroscopy. The oxidation catalytic of methyl phenyl sulfide
with the complexes in solution and heterogeneisated by means of supporting on alumina was
studied. The catalytic reactions were accompanied by gas chromatography; the catalytic
products were characterized by 1H Nuclear Magnetic Resonance and Fourier Transformed
Infra-red spectroscopy. The product of catalytic reaction, methyl phenyl sulfoxide, can be
Preface xi
used as an intermediate in the fabrication of pharmaceuticals. The oxovanadium (IV) complex

from the Schiff base [N,N’-bis(salicylidene)-1,3-xylylenediamine] presents the best catalytic
activity in homogeneous system probably due to its flexibility that favors the access of the
substrate to active center in the catalysis.
Chapter 9 – The use of soluble supports leads to recyclable catalyst systems that do not
suffer from mass transfer limitations, and therefore they should lead to systems with activities
similar to their monomeric analogues. Catalysis seems to be a research area in which
promising applications for dendrimers may be developed. Indeed, dendritic catalysts are
nanosized, and as such they are, as biomolecules, easily isolable from homogeneous reaction
media by precipitation, filtration, ultrafiltration or ultracentrifugation. In particular,
dendrimers have recently attracted a lot of attention, since these well-defined macromolecular
structures enable the construction of precisely controlled catalyst structures. This combination
of features makes dendrimers suited to close the gap between homo- and heterogeneous
catalysis, or, in other words, dendrimers will combine the advantages of homo- and
heterogeneous catalysis. Dendrimers have a number of potential applications, but the present
chapter is specifically focus on summarizing the major concepts for their properties as well as
the most pronounced advances for their applications as supports for recoverable catalysts and
reagents in asymmetric synthesis. This chapter highlights some of the notable examples of the
catalytic reactions using supported dendritic catalytic systems in such reactions as
hydrogenation, hydroformylation, alkyation, epoxidation, dialkylzinc addition to aldehydes
and imines, Heck and other Pd-catalyzed C-C bond formation. The intriguing properties of
dendrimers in catalysis including activity, selectivity, stability, and recyclability will be
addressed. Further key issues in this chapter relate to the deviating properties of dendrimers
as compared to their linear macromolecular counterparts is considered.
Chapter 10 – In view of the increasing environmental and economical concerns, it is now
imperative for chemists to invent as many environmentally benign catalytic reactions as
possible. Successful completion of reactions involving lipophilic and hydrophilic reactants
can be achieved by employing an environmentally benign technology viz., ‘‘phase transfer
catalysis’’ (PTC). Some of the prominent features of the PTC include, improved reaction
rates, lower reaction temperatures and the absence of expensive anhydrous or aprotic
solvents. Owing to its simplicity and the low cost of most of the phase transfer catalysts, the
PTC technology has found universal adoption. As a result, PTC is considered to have great
potential for industrial-scale application. Nowadays, due to these salient features, it has
become an important choice in organic synthesis and is widely applied in the manufacturing
processes of specialty chemicals, such as drugs, pharmaceuticals, dyes, perfumes, additives
for lubricants, pesticides, monomers etc. Due to ever increasing necessity of increasing the
efficiency of PTC in industries, researchers incessantly invented new and novel phase transfer
catalysts with more active-sites and higher efficiency. Asymmetric phase-transfer catalysis
has attracted considerable attention as a convenient technique for the synthesis of chiral
molecules. Cinchona alkaloids and ephedrine derived catalysts are the most popular chiral
PTC that has been employed to achieve the goal for inducing asymmetry into product
molecules. Currently, ingenious new analytical and process experimental techniques viz.,
ultrasound and microwave irradiation assisted PTC transformations have become immensely
popular in promoting various organic reactions. Phase transfer catalysis will be of curiosity to
anyone working in academia and industry that needs an up-to-date critical analysis and
summary of catalysis research and applications. In view of the success and vitality of this
xii Andrew C. Poehler
technique, the authors have proposed to present recent happenings in the field of PTC and to
study its applications to various organic reactions. Typical applications of PTC in silent,
ultrasonic and microwave conditions are described. Further, kinetics of various organic
reactions catalyzed by PTC carried out under a wide range of experimental conditions will be
presented.
Chapter 11 – Some C6 unsaturated alcohols, aldehydes and acids are widely used in
perfume chemistry. The easiest method for the preparation of hexenoic acids from the point
of view of selectivity and simplicity is the selective hydrogenation of easily available sorbic
acid (trans,trans-hex-2,4-dienoic acid). Depending on the catalyst used different regio and
stereoisomers, can be obtained in various mixtures.
From hexenoic alcohols the most commonly used compounds of this type are the so-
called “leaf alcohols”, specifically cis-hex-3-en-1-ol and trans-hex-2-en-1-ol. These
compounds can be prepared by selective hydrogenation of the sorbic alcohol obtained for
example from the chemical reduction of sorbic acid.
Details of the preparation of these compounds by hydrogenation using heterogeneous
catalysts are given elsewhere [1-4]. The major disadvantages of the use of heterogeneous
catalysts in this case are the low selectivity of the process (in the case of hex-3-enoic acid
derivatives there is essentially no selectivity) and the use of sorbic acid itself is impossible.
Instead salts or preferably methyl or ethyl esters are used, introducing another step to the
process. The use of homogeneous catalysts opened new possibilities to carry out the
hydrogenations and significantly higher selectivities of formation of the desired products.
As stated above hexenoic acids and alcohols have very interesting fragrant properties.
The titling of the two hexenols as leaf alcohols is partly reflective of their smell – their
fragrance resembles that of freshly cut grass. Perfumers [5] define their fragrance a little more
precisely: cis-hex-3-en-1-ol is specified by its intense smell of fresh grass, it is a component
of geraniol, lavender and brandy mint oil, it is added to flower aromas (lilac for example) and
it can be used in imitations of mint and different fruit mixtures. trans-Hex-2-en-1-ol has in
low notes a strong fruit smell (chrysanthemum or wine), it is sweeter and more fruity than cis-
hex-3-en-1-ol and it is often used as a component of artificial strawberry. It is also used for a
refreshing orange aroma and it is a component of artificial geraniol and lavender oil. trans-
Hex-2-en-1-oic acid has a warm fruit aroma after dilution, partly herbaceous and slightly
acidic. It is used as an imitation of raspberry or in many other fruit aromas that require a
caramel-acid note.
The fragrant properties of hexenoic aldehydes are also very interesting for the perfume
industry but the simplest method of preparation (aldol condensation) was not superseded by
hydrogenation due to the low stability of aldehydes.
Chapter 12 – Homogeneous modification of sugarcane bagasse cellulose with succinic
anhydride (SA) was catalyzed with three different catalysts including iodine, N-
bromosuccinimide (NBS), and 4-dimethylaminopyridine (DMAP) in a solvent system
containing 1-butyl-3-methylimidazolium chloride ionic liquid ([C4mim]Cl) and
dimethylsulfoxide (DMSO). The effects of the mass ratio of catalyst/SA, reaction time, and
reaction temperature on the degree of substitute (DS) of cellulose were investigated. The
results showed that the DS of cellulosic derivatives increased to 0.56-1.54 under the
experimental conditions catalyzed with iodine, 0.92-2.31 with NBS, and 0.94-2.34 with
DMAP, from 0.24 without any catalysts, indicating that these three catalysts were effective
catalysts for cellulose succinoylation in ionic liquids. The possible mechanism of
Preface xiii
homogeneous succinoylation catalyzed with these catalysts and the actual role of these
catalysts were also investigated. Fourier transform infrared and solid-state cross-
polarization/magic angle spinning 13C NMR spectroscopies also provided evidence of
catalyzed homogeneous succinoylation reaction. The results indicated that the reaction of
hydroxyl groups at C-6, C-2, and C-3 positions in cellulose occurred.
Chapter 13 – The knowledge of the efficient formation of C−X (X = C and N) bonds
asymmetrically or otherwise is vital to contemporary organic synthesis. In this context
notable is the contribution of Pd towards the development of the area. The specialty of Pd as a
metal lies in its ability to efficiently construct numerous types of C−X (X = C, N, O and S)
bonds under ambient conditions. A key strength of Pd mediated synthesis thus lies in its
chemo- and regio selectivities that facilitate the synthesis of intricate target molecules
otherwise not conveniently accessible by traditional methods. Furthermore, Pd, being a late
transition metal, inherently possesses important attributes like, the air and moisture stability
and the functional group tolerance, which often are the key ingredients of a successful
catalyst. Of late, the N-heterocyclic carbenes (NHC) have added a new chapter in the design,
discovery and development of Pd catalysts, thereby generating an enormous interest in its
palladium complexes in recent years. The strong σ-donating nature of the N-heterocyclic
carbene ligand in the catalyst allows oxidative insertions of challenging substrates while the
ligand topological steric demands promote the fast reductive elimination reactions, which
together constitute two important steps in numerous catalysis cycles. Additionally, the strong
palladium−N-heterocyclic carbene (Pd−NHC) interaction help stabilizes many catalytically
important active species at low ligand to Pd ratios and also at high temperatures thereby
broadening its scope of catalytic applicability. Apart from the C−X (X = C and N) bond
forming reactions, the Pd complexes of N-heterocyclic carbenes perform various other
reactions like the oxidation reactions, Tsuji-Trost reaction and the polymerization reactions
etc. Even extending further beyond chemical catalysis, the palladium N-heterocyclic carbene
complexes exhibit promising potential in various biomedical applications like in the
anticancer studies.
Chapter 14 – The application of metal-complex catalysis opens the possibility of
regulating the relative rates of elementary stages Cat–O2, Cat–ROOH, Cat–RO2 and in that
way of controlling the rate and selectivity of processes of radical-chain oxidation [20]. By
changing the ligand environment of the metal center or adding different activating
compounds, it is possible to vary the yields of target products, and thus control the reaction
selectivity.
The catalyst performance is always accompanied by its deactivation. It should be
mentioned that in its original form, a catalyst often represents only the precursor of real
catalytic particles. By introducing various ligands-modifiers into reaction, it is possible to
accelerate the formation of catalytically active species and prevent or hinder the processes
that lead to catalyst deactivation. Understanding of the mechanisms of the additive’s action at
the formation of catalyst active forms and mechanisms of regulation of the elementary stage
of the radical-chain oxidation may apparently lead to the development of new, efficient
catalytic systems and selective oxidation processes.
In: Homogeneous Catalysts ISBN: 978-1-61122-894-6
Editor: Andrew C. Poehler © 2011 Nova Science Publishers, Inc.
Chapter 1
METALLIC NANOPARTICLES NANOCOMPOSITES:

THEIR CATALYTIC APPLICATIONS
Rocío Redón*, N. G. García-Peña and F. Ramírez-Crescencio

Centro de Ciencias Aplicadas y Desarrollo Tecnológico
Universidad Nacional Autónoma de México, Cd. Universitaria
A.P. 70-186, C. P. 04510, Coyoacán, México D. F., México.
ABSTRACT
More than a simple review, this is a compilation of what has been done so far in
relation to metallic nanoparticle-polymer composites with applications in catalysis
reported up to now. We are going through all the transition metals from scandium to the
noble metals to the copper group. Also, we report that, basically, the noble or platinum
group metals are the metals commonly used as catalysts although some of the others have
been proven to work as catalysts on different reactions.
INTRODUCTION
Nanocomposites can be defined as nanomaterials that combine one or more separate
components in order to obtain the best properties of each component in which nanoparticles
act as fillers in a matrix, usually a polymer matrix. In catalysis, in particular, metal
nanoparticles act as catalysis centers, while the matrixes are the supports of these centers,
trying to obtain materials that can have both properties as large, recoverable and reusable
supports but with plenty of reaction centers, like in heterogeneous catalysis, which can be
soluble obtaining the benefits of homogeneous catalysts.
Since nanoparticles have high relationship superficial area/volume which gave them their
different properties compaired from their macromolecular counterpart; they are so reactive
*
Corresponding Author Rocío Redón, telephone +52-55/5622-8602, ext. 1154; FAX +52-55/5622-8651, E-mail:
rredon@unam.mx.
2 Rocío Redón, N. G. García-Peña and F. Ramírez-Crescencio
that it is necessary to protect them by adding extra molecules such as polymers or dendrimers
and they can have either inter- or intra-molecular interactions or a combination of both
(Figure 1).
Inter-molecular interactions
= Metallic NPs Intra-molecular interactions

= Matrix molecules (Chemical bond)
Figure 1. Possible interactions in Nanocomposites.
Sc-Mn groups
The first elements that we are going to address, are from the groups scandium to
manganese, which basically, can produce metal oxides and usually are employed as supports
of other metallic nanoparticles, thus in this part we are going to mention a few researches, that
include the above mentioned metals and their applications.
Titanium. No information about synthesis of Nb nanocomposites has been found during
the present review. On the other hand, it is well known that titanium has been largely used as
titanim oxide as catalyst support, basically for heterogeneous catalysis, and in this direction
there are some researches that include gold metallic nanoparticles as catalyst centers, where
the authors fount that, the high catalytic activity of SSP-Au/TiO2 1073 is attributed to the
highly dispersed gold particles being modified by a strong interaction with TiO2 that induced
a synergy effect in the catalysis [1], some others only report the synthesis of the
nanocomposites TiO2-metallic NPs [2], or the main research is around some optic
applications, like in the Murray´s paper, where they report spectral features of far-infrared
electromagnetic radiation absorption in anatase TiO2 nanopowders that they attribute to
absorption by acoustic phonon modes of the dispersed nanoparticles [3]; as corrosion
protective. A TiOx porous layer obtained by templating synthesis was used as nanostructured
reservoir for an organic corrosion inhibitor. This provides active corrosion protection and
self-healing ability of the coating system [4]; finally, we have found a example where
titanium NPs are use in medical applications where the authors reported a increased skeletal
muscle cell and osteoblast numbers on hydrothermally-treated nano-hydroxyapatite/collagen
type i composites for entheses applications [5].
Metallic Nanoparticles Nanocomposites 3
The case of vanadium is similar to titanium, thus the reports include vanadium composite
as catalyst; the case presented is a metallic Ag arrays assembled in nanoporous VSB-5
nanocrystals, where the catalytic activity of these Ag(O)-VSB-5 composites was found to be
highly efficient catalysts for the syntheses of olefin aldehyde from styrene [6] and in optical
applications with vanadium oxide (VO2) in a study where they reported that the optical
contrast between the semiconducting and metallic phases is dramatically enhanced in the
visible region, presenting size-dependent optical resonances and size-dependent transition
temperatures [7a] in a study concerning the absorption and scattering of infrared radiation by
vanadium dioxide nanoparticles with a metallic shell, where the authors prove that the
transition of VO2 to the metallic state near (or away from) plasmon resonances leads to a
decrease (or increase) in the absorption and scattering cross sections for a given wavelength
[7b]; or in a material to build fiber-optic by using ion implantation to dope the VO2
nanoparticles with tungsten or titanium ions, where they demonstrated, the ability to control
the characteristics of the phase transition [7c]. In the case of chromium we only found reports
related to optical application with the use of aerosils modified by chromium oxide, where the
optical properties of the nanocomposites demonstrates that the obtained nanocomposites can
be used as passive Q switches [8]; or as an etch mask to fabricate pyramidal pits and then as a
deposition mask to form the metallic pyramids [9]
As in the previous elements, manganese also has been used as manganese oxide as
support for gold NPs, obtaining a synergistic catalytic effect on conversion and selectivity in
the case of Au/MnO2CeO2 catalysts, due to the coexistence of metallic and nonmetallic gold
species within nano gold particle and the minor presence of Ce3+ species [10]; on the
manufacture of new generation catalysts containing various metals (nickel, manganese,
copper, palladium) deposited on a porous support such as alumina or silica gel, which in the
case of asymmetric catalysts, Pd nanoparticles associated to cinchonidine as an asymmetric
ligand inside silica particles have been prepared by this process for the ethyl pyruvate
hydrogenation [11]; or for the production of carbon nanotubes with marine manganese nodule
as a versatile catalyst, where the catalytic metal cations, originally accommodated in the
mineral, moved to the outer surface, where they aggregated to metallic nanoparticles available
for the growth of the nanotubes [12] and just, synthesized for future applications [13].
In the last years, yttrium has become an important constituent of various materials for
technical applications [14] and a wide range of articles have been published, essentialy as
Y2O3, (yttria) [15] and yttrium aluminium [16] (or iron [17]) garnet nanoparticles.The only
example that we found reported related to metallic yttrium involves an Al–Y–Ni–Co–Pd alloy
achieved by the group of Louzguine-Luzgin [18].
Many of the articles about Zirconium and nanoparticles are more related with ZrO2
(zirconia) as an excellent support of other nanostructures [19]. Although, some investigations
about metallic nanostructured zirconium have been informed. Bulk metallic glasses based on
zirconium NPs had attracted great attention due to their elastic strain and remarkable
plasticity [20]. J. B. Qiang et. at. [20] have prepared an alloy ingot with a composition
Zr65Al7.5Cu27.5. Hajlaoui et. al. [21] reported an Cu50Zr50 alloy. And the group of Eckert [22]
has achieved Zr62-xTixCu20All0Ni8 bulk samples (0 ≤ x ≤ 7.5). Other examples of alloys as
Dutkiewicz’s [23] can be found. S. P. Gubin [24] and collaboratores reported a metallic
zirconium-poly(carbosilane) nanocomposites.
As in the case of scandium, no information about synthesis of Niobium nanocomposites
has been found during the present review. Metallic niobium particles are reported only in
alloys; generally with Fe and B [25]. In addition, some investigations have been made on Nb
as support of magnetic Tb nanoparticles [26]; as thin films [27] or matrix [28]. Physical
techniques of synthesis were used when metallic molybdenum NPs were required. V. S.
Purohit [29] has obtained NPs through microwave assisted electron cyclotron resonance
(ECR) plasma induced chemical sputtering process, using hydrogen as the ionizing gas, with
particle sizes of 6-7 nm.
Molybdenum nanocomposites are more usual than “naked” or not protected NPs, due to
their reactivity with environmental oxygen. Berko’s group has achieved Mo nanoparticles on
a TiO2 (1 1 0) surface trough molecular vapor deposition (MVD) [30]. Other studies, like
Pétigny ‘s [31], Blondeau-Patissier [32], Domenichini’s [33], Prunier’s [34], or Petukhov’s
[35] are focus on this system. L.A. Díaz et. al. [36] have obtained alumina/molybdenum
nanocomposites putting together α-alumina powder and MoCl5 in anhydrous ethanol. Unlike
physical techniques, little information about synthesis of metallic molybdenum NPs by soft
chemical reduction is found. Redel’s group had obtained dispersions of this metal through
thermal decomposition of Mo(CO)6, using ionic liquids (ILs) as stabilizers [37].
Technetium. 99mTc is widely used in radiopharmaceutical for diagnosis and therapeutic
purposes [38] mainly as coordination compounds [39]. Fortunatelly, some reviews of 99mTc
nanocomposites are reported [38-40], where the authors inform that these NPs have
compositions based on TcxSy.
Only a few reports have ben found related to lanthanum NPs, like the one from Cao et.
al. [41], who informed a method for preparing graphitic carbon encapsulated lanthanum NPs.
On other paper, lanthanum hydroxide nanofibers have been synthesized by Djerdj et. al. [42]
Fokema and Ying [43] have synthesized La2O3 through an aqueous solution of La(NO3)3
added to an aqueous organic base and aged for 12-24 h. This oxide presented a catalytic
activity for NOx reduction with methane in the presence of oxygen. Peng et. al. [44] have
obtained Lanthane-doped mesoporous TiO2 nanoparticles via hydrothermal process by using
cetyltrimethylammonium bromide (CTAB) as surfactant-directing agent and pore-forming
agent. Mesoporous doped TiO2 nanoparticles have mean diameter of 20 nm with mean pore
size of 2.2 nm and show activity on the oxidation of rhodamine.
As the rest metals in these grops, hafnium has been studied as de correspondant, in this
direction B. Reddy and coworkers [45] have synthesized nanocomposite oxides of CeO2-
HfO2, for soot oxidation. Silica-Hafnia nanocomposites have been obtained by Loureiro et. al.
[46] Nanoparticles of HfO2 have been obtained through ultrasonically assisted hydrothermal
decomposition of HfO(OH)2.nH2O by Meskin et. al. [47] Reactions of hafnium isopropoxide
with hafnium halides at high temperature in pure TOPO (Trioctylphosphine oxide) yield
nanometer-sized HfO2 nanocrystals of 5.5 nm [48].
Nano-tantalum powders have been prepared by arc-plasma method and the average
diameter of the grains is 10 nm [49] the product consist of a large quantity of nanoparticles of
tantalum and hexagonal δ–TaO phase. Schulz et. al. [50] have obtained Ta2O5/SiO2 particles
by flame spray pyrolysis (FSP). On other investigations, oxides of tantalum have been
synthesized by thin-wire explosion [51], non-aqueous condensation of tantalum ethoxide [52],
and hydrolysis of tantalum ethoxide [53]. Tantala-coated polystyrene (PS) particles were
prepared by hydrolyzing tantalum ethoxide in ethanol at 28 °C in the presence of
functionalized PS beads (540 nm), the polymer core was removed either via chemical
treatment with toluene or calcination at 650 °C obtaining sub-micrometer hollow spheres of
Ta2O5 [54].
Sahoo and coworkers [55] have obtained tungsten nanoparticles by thermal

decomposition of tungsten hexacarbonyl [W(CO)6] at 160 °C in presence of a mixture of
(1:1) surfactants, oleic acid and trioctyl phosphine oxide (TOPO) under a blanket of Ar gas.
The presence of surfactant reduces the particle size and with further increase in surfactant
concentration increases the particle size. Tungsten NPs [56] are obtained reproducibly by
thermal or photolytic decomposition under argon from mononuclear metal carbonyl
precursors M(CO)6 (M = Cr, Mo, W) suspended in the ionic liquids BMim+BF4-, BMim+OTf-
and BtMA+Tf2N- (BMim+ = n-butyl-methyl-imidazolium, BtMA+ = n-butyl-trimethyl-
ammonium, Tf2N = N(O2SCF3)2, OTf = O3SCF3) with a very small and uniform size of 1 to
1.5 nm in BMim+BF4- which increases with the molecular volume of the ionic liquid anion to
~100 nm in BtMA+Tf2N-. A mixture of scheelite (CaWO4) and magnesium was milled
together for 100 h in a nitrogen atmosphere, after removal subproducts, 10 nm crystallites of
elemental tungsten were obtained [57]. Thermal plasma process was applied by Ryu et. al.
[58] to produce nanosized tungsten powder using ammonium paratungstate (APT) as the
precursor. The produced tungsten powder was treated by hydrogen during which minor
amounts of WO2 or WO3 were reduced to tungsten. Finally, nanosized W powder consisting
of spherical particles of less than 50 nm was obtained. WO3/TiO2 composite NPs have been
synthesized by dissolving W and Ti precursors in a suitable solvent and spraying into a high
temperature acetylene-oxygen flame using a reactive atomizing gas, obtaining sizes from 5 to
20 nm and 10 to 50 nm. Additionally WO3/TiO2 has been successfully tested for selective
catalytic reduction of NOx. [59], with good results. WO3/polyacrylonitrile nanocomposite
were obtained by Wei et. al. [60] stirring WO3 nanoparticles in a commercially available
polyacrylonitrile (PAN) solution. Makaryan [61] have studied the synthesis of composite
polymer-based materials. Polymeric matrices chosen are the copolymer of formaldehyde and
dioxalane (CFD) and the polyphenylene sulphide (PPS). Results indicate a higher hardness
using amorphous nanosized tungsten fillers with a particle size less than 10 nm.
Rhenium nanostructures have been synthesized by Hassel and coworkers [62]. A NiAl–
1.5 at.%Re eutectic alloy was directionally solidified using a constant growth rate and
temperature gradient. The selective dissolution of the NiAl matrix with a mixture of
HCl:H2O2 produced rhenium fibers (diameter ~400 nm) Digestion of the NiAl–Re eutectic in
sulphuric acid, on the other hand, produced mainly long rhenium fibres. On the other hand,
rhenium sulfide nanoparticles have been obtained by Tu et. al. [63].
FE-CU GROUPS
These are the main metals that had ben involved in catalysis since the catalysis was
explored, thus we are going to try to cover the newest publications on the nanocomposites
metal NPs-support molecule and their catalytic applications.
In the last years, iron has become more important in catalysis, especially in within the
employment of nanoparticles, thus we are going to mention some of the last papers related on
nanocomposites that contain iron nanoparticles and their uses mainly on catalysis, even
though there are some other applications like in magnetism or optical, which will be mention
also.For example they had been used supported on carbon nanotubes in during Fisher-
Tropsch synthesis [64]; in the decomposition reaction of H2O2 by measuring the formation of
gaseous O-2, using a Fe-0/Fe3O4 composite [65]. Fe/SBA-15/carbon composites were used as
catalyst in the benzylation reaction of benzene with benzyl chloride [66]; as model catalyst Fe
film on SiO2 during preannealing in O-2 and NH3 and during C2H2 decomposition, where the
catalyst metal surface supplies sites to dissociate the hydrocarbon precursor and then guides
the formation of a carbon lattice and the liftoff of a carbon cap. The Fe the active state of the
catalyst is a crystalline metallic nanoparticle, while graphitic networks do not form on
oxidized Fe [67a]; in the synthesis of carbon nanotubes (CNT), by using a nanocomposite of
montmorillonite clay through anchoring on FeCo nanoparticles [67b] or by using Fe-doped
carbon aerogels [67c]; by employing ferrocene, yielding nanofiber-supported iron oxide
nanoparticles, while secondary carbon nanofibers with diameters in the range from 10 to 20
nm were subsequently grown from cyclohexane catalyzed by the sintered metallic iron
nanoparticles under reducing conditions [67d]; in the case of metallic iron particles in
montmorillonite matrix, to obtain a catalytic conversion of phenol oxidation of 49.5 % with a
67.4 % of selectivity to carbon dioxide and tar, where the authors propose that the iron
species dispersed in clay matrix may provide the catalytic active sites and the size of iron
species has an effect on selectivity [68]; as support like iron oxide with gold NPs in methanol
oxidation, obtaining an enhanced oxidation with the use of this support [69]; in microwave
oxidation of alcohols using supported metallic iron nanoparticles [70]. Most of the reports are
related with the magnetic [71-82]; optical properties [83], as templates [84]; dissecants; in the
design of permeable reactive barriers [85]; as humidity sensors [86] or only the synthesis of
iron nanocomposites for future applications [87-96].
The reports that we have found for cobalt nanocomposites are some related to magnetic
applications [97-99] and one more related to the synthesis for future applications [100]. The
case of nickel, as in its bulk applications, there are more catalysis examples; in their use as
catalysts in Sonogashira coupling reactions [101]; in methanation, with silica supported Ni
NPs, where the nanoparticles were more efficient without the support [102]; in order to
understand the oxidation of the nanoparticles surface when catalytic reactions take place and
to understand more of the enantioselective heterogeneous catalysis, the authors made a study
with nickel NPs and tartaric acid [103]; there are also some papers related to magnetic
applications [104-107] and those dedicated on the nickel nanocomposite synthesis [108-113].
There are some papers dedicated to copper NPs catalysis, such is the case of the reactions to
produce Hydrogen by reforming of methanol in supercritical water; in this paper the authors
reported the in sittu generation and regeneration of the Cu NPs catalyst [114]; in the Ullman
reaction with sonochemically derived copper powder that shows the presence of porous
aggregates (50-70 nm) which contain an irregular network of small nanoparticles. The as
prepared copper NPs are catalytically active toward the mentioned "Ullmann reaction"-that is,
the condensation of aryl halides to an extent of 80-90 % conversion [115]; on other paper, the
authors reported that copper metallic particles are formed and get anchored in the siloxane
oligorner obtained during the reaction of phenylsilane and ethyleneglycol with bis-
pyridinium, tetrachlorocopper(II). These supported metallic copper particles can catalyse the
coupling reactions of silanes with alcohols [116]; Finally, the use of copper NPs, in this case
deposited onto mesoporous SBA-15 support were proved in catalytic activity tests for CO
oxidation, where the best performance was obtained when the catalyst was calcined at 500 °C
and reduced at 550 °C [117]. The rest of the papers that we have found are related to other
applications such as optical [128-124]; as combustion characteristics [125]; as insulators
[126]; as cathode material [127]; studing their mechanical properties [128], and there are
those related to the synthesis of copper nanocomposites [129-133].
Ruthenium catalysis. Metallic ruthenium NPs are used in the catalytic hydrogenation of
unsatured bonds. Marconi et. al. tested γ-Al2O3 supported metallic ruthenium nanoparticles in
the catalytic hydrogenation of methyl benzoate to methyl cyclohexanoate, and 2-(4-
carbomethoxyphenyl)-1,3-dioxane to 2-(4-carbomethoxycyclohexyl)-1,3-dioxane [134]. For
methyl benzoate, the best results were found for the Ru-TOA supported on γ-Al2O3 using
cyclohexane as solvent, with a quantitative reaction in 8 h; and, in the case of 2-(4-
carbomethoxyphenyl)-1,3-dioxane, the same catalyst was reported as the most catalytically
active, with a quantitative reaction in 20 h, using tetrahydrofuran (THF) as solvent. In the last
case, the authors performed a modified catalytic test in solventless conditions, and lower
times of reaction (15 h) were achieved, though they found less selectivity of the desired
product (95%). Recently, Raspolli Galletti et. al. have developed γ-Al2O3 supported
ruthenium(0) NPs to catalyze the hydrogenation of phenol [135]; which has shown a catalytic
activity up to 88% conversion in 2 h, and a selectivity of 83% to cyclohexanone product
(cyclohexanol is the only byproduct). In a previous work, they have explored the synthesis of
this catalysis via polyol method assisted by microwave irradiation [136]. In this case, the best
result was achieved with 81.5% conversion in 2 h, with 87% selectivity to cyclohexanone
product. Chaudret group obtained ruthenium nanoparticles supported onto nanoporous
alumina membranes, and tested them in the catalytic hydrogenation of 1,3-butadiene in the
gas phase [137]; they have determined better activities for the nanoparticles pre-reduced and
later supported due to regularity inside the pores. Quantitative conversion was achieved in 25
minutes when 5 nm particles are used. Recently, Han’s group used a PVP (poly
(vynilpyrrolidone)) modified silica to support ruthenium nanoparticles [138]. A Ru/silica
catalyst was tested too in the hydrogenation of benzene under biphasic (ionic liquids-benzene)
conditions. Quantitative conversions were achieved in almost every case with TOF up to
74900 h-1, when the silica modified PVP support is used. Boujday and collaborators have
used a SBA-15-type mesoporous silica to introduce the [⎨Ru-(C6Me6)⎬2Mo5O18
⎨Ru(C6Me6)(H2O)⎬] poly-oxomolybdate by wetness impregnation, using dichloromethane as
solvent, reduce under a reducing atmosphere, and finally test it in the catalytic hydrogenation
of benzene [139]; with better catalytic activity at 623 K. Su and collaborators have
synthesized silica, carbon coated silica, and templated mesoporous carbon supported
ruthenium(0) nanoparticles [140]. When these catalysts were tested in the hydrogenation of
benzene and toluene, almost quantitative conversions were achieved in almost every
experiment with TOF up to 37.7 h-1, for benzene, and 9.8 h-1 for toluene. The Tsang’s group
used CO2 supercritical microemulsions to synthesize Ru nanoparticles [141]. These NPs were
tested in the reduction of citral. Quantitative conversion is achieved when the ruthenium
composite is used, with 75.5% selectivity for the citronellal (CIAL) product. In contrast,
Manikandan and co-workers obtained less selectivity and a major dispersion of products,
from 11% to 43% (geraniol, nerol, citronellal and citronellol, as principal products), for the
hydrogenation of citral when two montmorillonite supported ruthenium catalysts were used
[142]. Liu’s group has used the 1,1,3,3-tetramethylguanidinium trifluoroacetate
([TMG][TFA]) ionic liquid to support metallic ruthenium nanoparticles on montmorillonite
(MMT) [143]. In the hydrogenation of benzene, better results were obtained in comparison
with other catalysts (Ru/C and Ru/Al2O3) prepared by the authors. Quantitative yields were
reported at 40º C, in 1.5 h, and a TOF of 667 h-1. In a similar synthesis, Kantam and co-
workers obtained nano-crystalline magnesium oxide supported ruthenium nanoparticles,
using chlorine hydroxide ionic liquid, and used them in the transfer hydrogenation of various
carbonyl compounds [144]. 95% conversion of acetophenone to 1-phenylethanol (acetone as
by product) was achieved in 6 h. Asedegbega-Nieto and co-workers have supported
ruthenium nanoparticles onto carbon nanofibers with different topographies and used them to
hydrogenate selectively 4-acetamidophenol (paracetamol) [145]. During the catalytic
hydrogentation, the main product was a mixture of cis- and trans-4-acetamidocyclohexanol
with conversion of 60%; the best trans-/cis- ratio (1.4) is achieved when the ruthenium
nanoparticles are supported onto the platelet-like carbon nanofiber. In the same line of
investigation, Takasaki and collaborators used carbon nanofibers to support ruthenium
nanoparticles and used them in the partial hydrogenation of 1,1’-bi-2-naphthol (BINOL)
derivatives [146]. The best results were achieved for BINOL with a substrate/catalyst ratio of
1390, at 50º C, in 48 h, with a 99% yield of isolated 5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-bi-2-
naphtol (ee of >99.9%). In a previous work, this group used carbon nanofibers with different
topographies as supports, and applied these catalysts in the hydrogenation of toluene [147].
There, the authors determined that the best support is the platelet-type carbon nanofiber with
a quantitative conversion of toluene to methylcyclohexane with a TOF up to 14200 h-1. By
their way Zhao’s group, employed templated porous carbon materials to obtain supported
ruthenium nanoparticles, and used them to catalyze the hydrogenation of benzene [148].
Almost quantitative conversion (99.8%) is achieved when a benzene/Ru(0) ratio of 10000 is
used, in 1.0 h, at 110º C, and a TOF of 9980 h-1. Other group that has used carbon to obtain a
Ru(0) catalyst, is Denicourt-Nowicki et. al. [149]; the catalysts were tested in the catalytic
hydrogenation of o- m- and p-xylene. Superior results were obtained when randomly 3-
methyladed-β-cyclodextrin is used as stabilizer in the catalytic hydrogenation of m-xylene,
with 30.5 h-1 TOF, and 88.6% selectivity for the cis-1,3-dimethylcyclohexane, thought better
selectivity is achieved with the correspondent α-cyclodextrin with o-xylene. In a recent
investigation, the same group combined randomly methylated cyclodextrins and N,N-
dimethyl,N-hexadecyl,N-(2-hydroxyethyl)-ammonium chloride salt to form an inclusion
complex and stabilize metallic ruthenium nanoparticles, which were used in the catalytic
hydrogenation of arenes [150]. The best TOF (83.3 h-1) was achieved for the hydrogenation of
styrene, when β-cyclodextrin is used as part of the inclusion complex, though only the alkene
is reduced. When longer times are used in the catalytic reaction, the reduction of aryl group is
achieved. In other work, this group developed the stabilization of Ru(0) NPs by the random
methyladed cyclodextins [151]. In this investigation, the catalysts were tested in the catalytic
hydrogenation of alkenes, and in every case, quantitative reactions were achieved in different
times. The best results were for cyclohexene with a TOF of 34 h-1, when 3-methyladed-β-
cyclodextrin is employed. A previous work from this group focused in the stabilization
efficiency of the methylated cyclodextrins, and realized the first attempts to apply these
ruthenium NPs in the catalytic hydrogenation of aryl derivatives [152]. In every case, the
reaction was quantitative, with superior results for benzene with 25h-1 TOF, if the metylated-
β-cyclodextrin is used as stabilizer. On the other hand, Sun et. al have used a series of Y
zeolites (PQ-13.6, LZY-82 and a dealuminated DLZY-82) to prepare zeolite supported
ruthenium NPs by ion exchange and subsequent reduction in a H2 flow [153]. These catalysts
were compared with their sulfide analogous, and the authors reported lower catalytic
properties, yet better selectivity toward the formation of isomerisation products. Philippot,
Roucoux and Claver’s group have developed an interesting oncoming to enantioselective
catalysis [154]. In a homogeneous catalysts approach, they have used furanose derived
diphosphite ligands as stabilizers. The catalyst was tested in the catalytic hydrogenation of o-
and m- methylanisol; in the first case, quantitative hydrogenation was achieved in pentane, at
20º C, with 100% selectivity for the cis-1-methoxy-2-methylcyclohexane product, with a
TON of 98; and in the second case, quantitative conversion was fulfilled in pentane, at 20º C,
79% selectivity for selectivity for the cis-1-methoxy-3-methylcyclohexane product, with a
TON of 98. In the same way, Dupont’s group has achieved metallic NPs in ionic liquids, they
have used 1-n-butyl-3-methylimidazolium (BMI) and 1-n-decyl-3-methylimidazolium (DMI)
N-bis(trifluoromethanesulfonyl)imidates (NTf2) an tetraflouroborates (BF4) ionic liquids to
synthesize well dispersed metallic ruthenium nanoparticles by [Ru(COD)(2-methylallyl)2]
decomposition under H2 flow at 50º C [155]. These stabilized NPs were used in the catalytic
hydrogenation of arenes in biphasic conditions, and superior result were obtained for toluene
when [BMI][BF4] is used as stabilizer, with a 85% of conversion to methylcyclohexane in 18
h at 75º C. In contrast, when the hydrogenation of more substituted benzenes are carried out,
low conversions are achieved. By their way, Rossi et. al. used RuO2 as precursor to
synthesize Ru(0) nanoparticles in ionic liquids [156]; with a quantitative conversion and a
TOF of 953 h-1. A lower, but still good, TOF is achieved for toluene with 556 h-1 in the same
conditions. When it comes to colloidal nanoparticles, Lu et. al. achieved PVP protected
nanoparticles and used them in the catalytic hydrogenation of arenes, olefins and carbonyl
compounds [157]. Quantitative conversions were achieved in every case, with superior TOFs
from 1,100 h-1, for methylbenzoate, to 45,000h -1, for benzene. Finally, the hydrogenation of
carbon monoxide to yield hydrocarbons (Fischer-Tropsch process) was reported by Kou and
Yan’s group [158], where an activity up to 1.6 h-1 has been achieved for the reaction carried
out in water, using NaBH4 as reducing agent. A more recent investigation is reported by Kang
et. al. They have used supported ruthenium nanoparticles onto different supports to carry out
the Fischer-Tropsch process [159]. The best conversion (34%) of CO is achieved for the
modified carbon nanotubes supported ruthenium NPs, with 60% selectivity for C10-C20
hydrocarbons. Other colloidal ruthenium NPs were achieved by stabilization with
octa(aminophenyl) silsesquioxane (OAPS). Yang and collaborators carried out the
investigation [160]. The obtained NPs get poor TOFs (from 0 to 6 h-1) for the reduction of
phenylaldehydes. Pertici’s group have used inorganic polyorganophosphazenes to support
Ru(0) NPs and used them in the hydrogenation of various unsatured groups [161]. The
authors said that their catalyst is soluble in organic mediums, so the cataytic tests can be
carried out in biphasic or homogeneous mediums. When the catalysts were tested in the
reduction of olefins, better result is achieved for the hydrogenation of α-acetoamido acrylic
acid with a quantitative conversion to N-acetylalanine, with 16.7 h-1 TOF, in a biphasic
medium (catalyst/H2O). When tested in the hydrogenation of ketones, good results with 16.6
h-1 TOFs were achieved for the hydrogenation of ethyl pyruvate to ethyl lactate in a
homogeneous medium (ethanol). On the contrary, poor results are obtained when the catalyst
is employed in the reduction of aryl derivatives (3.3 h-1 TOF for p-aminomethyl-benzoic acid
to 4-aminomethylcyclohexane carboxylic acid with 3 cis-/trans- ratio). Other catalytic
reduction carried out by Ru(0) NPs is the hydrogenation of aromatic nitrocompounds.
Recently, Pietrowski an collaborators, who studied the reduction of o-chloronitrobenzene to
o-chloroaniline using magnesium fluoride supported ruthenium NPs as catalyst [162]. Zuo
group prepared SnO2 supported metallic ruthenium NPs and used them to catalyze the
hydrogenation of o-chloronitrobenzene [163]. When the Ru/SnO2 and Ru/PVP were tested for
the catalytic hydrogenation, similar values were reported: quantitative conversion with
>99.9% selectivity for the desired product. Other catalytic reaction that can be seen as
reduction is the catalytic ammonia decomposition. Some examples catalyzed by ruthenium
NPs are found. Zheng and collaborators prepared a series of γ-Al2O3 supported Ru(0) NPs, to
study kinetically the catalytic decomposition of NH3 [164]. With their catalysts, at 823 K, a
complete decomposition of NH3 is achieved. By their way, Yin et. al. have realized studies in
the catalytic decomposition of ammonia, using supported ruthenium NPs. In an article, they
have synthesized a series of ZrO2 materials modified with KOH and NH4-OH (labeled as
ZrO2-KOH and ZrO2-NH4OH, respectively) [165]. The ruthenium NPs were supported by
incipient wetness impregnation of the support materials using ethanolic [Ru(acac)3] solution.
The best conversion (58.2%) was achieved at 673 K, using the ZrO2-KOH supported
ruthenium chlorine free NPs. The catalysts obtained via RuCl3 showed poor activities,
proving chloride poisoning in the samples. In other work, this group supported ruthenium
NPs onto CNT through the same method and modified with KOH [166]. Besides, CNT, other
supports (MgO, activated carbon, ZrO2, and Al2O3) were employed to compare the catalytic
activities. A quantitative conversion was achieved at 550º C, with a H2 formation rate of 33.5
mmol/(g-catal min). In a process contrary to the hydrogenation of unsatured bonds, the
ruthenium NPs catalyzes the oxidation of molecules also. One of most reported processes is
the partial oxidation methane. Gedanken’s group studied the catalytic activity of SBA-15-
supported ruthenium NPs in the partial oxidation of methane [167]. The maximum conversion
of methane (65.4%) is achieved with a Ru loading ratio of 14 %, at 750º C with 83.5%
selectivity for the CO product. Latter, this group used a similar process to synthesize a
Ru/TiO2 mesoporous catalyst [168]; but in this occasion, ultrasound is used instead of
microwave irradiation. Better results were achieved in this experiment, with up to 88.5%
conversion of methane, with 95.5% and 95.8% selectivity to CO and H2, respectively, when
the reaction is carried out at 800º C. Other work focused in this catalytic reaction is the one
developed by Balint et. al. [169] The catalyst was obtained through a polyol process in
presence of γ-Al2O3. The best result is achieved at 650º C with a 79% conversion of the
methane, and 72.1% and 67.6% selectivity to CO and H2, each. In other experiment, the
group studied the dependence of the formation of equilibrium RuO2 ⇔ Ru at lower and
higher temperatures, on the formation of completely oxidized products and CO/H2 production
[170]. Concluding that higher temperatures, and consequently production of Ru(0), are
necessary for a good production of CO/H2(syngas). In a previous work, this group
investigated the partial reduction of methane, using NO as oxygen source [171]. The catalyst
used is the same, synthesized by the same method. At 650º C, the highest selectivity is
achieved with 81% and 82% for CO and H2, respectively. Other process catalyzed by
ruthenium NPs is the oxidation of arenes, via a wet air oxidation. Guerrero-Ruiz and
collaborators report this process [172]. The supports used were ZrO2 modified with SiO2,
mesoporous high surface area graphite (HSAG), and commercial activated carbon (AC). The
ruthenium NPs were loaded by impregnation of the supports with an excess of solvent (THF
and ethanol) volume in a rotatory evaporator with solutions of the precursors, dried, and
reduced under a H2 flow. In a comparative conversion of the arenes to CO2, the oxidation is
realized in absence of catalyst, 473 K is required to obtain 90% and 100%, for aniline and
phenol, respectively. When the supported catalysts were tested, up to 269 h-1 and 1232 h-1
TOFs were achieved, for aniline and phenol, respectively, with high mineralization yields,
when activated carbon is used in both cases. Perkas and co-workers developed a similar
method [173]. This group, supported ruthenium nanoparticles over mesoporous TiO2
(modified with dodecylamine) and ZrO2 (modified with sodium dodecyl-sulfate) with high
surface area, prepared by a sonochemical method. When the catalytic oxidation of acetic acid
was carried out, up to initial rate of 19.0 mol-acid/(h*mol-cat) when Ru/ZrO2 is employed; in
the case of oxidation of succinic acid, up to initial rate of 30 mol-acid/(h*mol-cat), when
Ru/TiO2 is used; finally, when p-coumaric acid oxidation was tested, rapidly disappeared to
yield p-hydroxybenzoic and p-hydroxybenzaldehyde acids, with Ru/TiO2, which were further
oxidized. Other process reported for the ruthenium NPs mediated catalysis, is the oxidation of
D-glucose to D-gluconic acid. Matveeva’s group developed a ruthenium catalyst for this
process [174]. The catalysts were prepared by impregnation of Ru(OH)Cl3 into a
hypercrosslinked polystyrene (HPS) matrix. Up to 13.8x10-3 s-1 TOFs are found for this
catalyst, with 99.6% selectivity for the D-gluconic acid product. Besides the decomposition of
ammonia, synthesis of ammonia is carried out by ruthenium NPs. Recently, Seetharamulu et.
al. have used two ruthenium alkali promoted catalysts supported onto Mg-Al hydrotalcite
(HT) [175]. The highest activity is reported for the double promoted catalyst, modified with
the polyol process, with more than 160 x 104 TOF; while the cesium promoted catalyst is
more active at lower temperatures. Moroz group used the cesium promoted ruthenium
catalyst, supported onto MgO, to also synthesize ammonia [176]. The catalyst was deposited
via two successive wetness impregnation methods of acetone Ru(OH)Cl3 and ethanol Cs3CO3
solutions. Superior activities were achieved for the cesium promoted catalyst in comparison
with the ruthenium catalyst. In the article, the authors try to explain these results. Recently, an
investigation of catalytic decomposition of NaBH4 to produce H2 via polystyrene
microspheres supported ruthenium NPs is reported by Chen and co-workers [177]. By their
way, Liu and collaborators had used a LiCoO2 supported ruthenium catalyst via a microwave-
assisted polyol process [178]. With 1 wt. % Ru/LiCoO2 loading, rate up to 0.05 L(H2)/(s
g(catalyst)) achieved. In the same line of investigation, Özkar group have prepared a Ru(0)
dispersion stabilized by sodium acetate by chemical reduction with NaBH4 [179]. Up to 7.9
s-1 TOF is achieved with this catalyst. Choi et. al. reported a series of polymer supported
ruthenium NPs to catalyze carbenoid transfer reactions [180]. When different α-
diazoacetamides are tested in the intramolecular carbenoid C-H insertion, N-p-chlorobenzyl-
N-tert-butyl-α-ethoxycarbonyl-α-diazoacetamide gave the best result, with a 98% yield of
isolated product, with an exclusive production of the cis-β-lactam, in 1 h, when the NCPS-Ru
catalyst was used. The authors report the catalytic production of γ-lactams by the catalytic
carbenoir C-H insertion of diazoacetamides derived from amino acids, using NCPS-Ru as
catalyst, too: when used the diazoacetamide prepared from L-phenylalanine, up to 90% yield
was obtained for the trans-γ-lactam. The intramolecular carbenoid N-H insertion reaction
catalyzed by NCPS-Ru was examined also: allyl diazoacetates gave proline products with
high cis- selectivity and in superior yields (91-96%). These substrates were tested in the
catalytic cyclopropanation, too: production of cyclopropyl lactones in good yields (70%-89%)
was achieved. When tested the catalytic intramolecular tandem ammonium ylide/[2,3]-
sigmatropic rearrangement reaction, up to 95% yields were achieved, with no [1,2]-
rearrangement product detected. This catalyst is active toward the intermolecular
cyclopropanation of alkenes, with up to 91% yield for styrene, with 70:30 trans-/cis- ratio. In
the catalytic intermolecular carbenoid N-H insertion high yields (99%-60%) were obtained by
a one-pot reaction of the appropriate amine and ethyl diazoacetate, even in scaling up
reactions. Finally, intermolecular carbenoid C-H insertions were tried: the reaction of methyl
phenyl diazoacetate with different substrates, up to 62% yield for only one product is
achieved. Selective aerobic epoxidation of alkenes is catalyzed by ruthenium NPs stabilized
by H5PV2Mo10O40 (POM) and supported by wet impregnation on α-Al2O3; this investigation
was developed by Neuman’s group [181]. Different alkenes were tested in the catalytic
epoxidation, and the best result was achieved when cyclododecene was used, with a 66%
epoxide yield. No other products beside epoxide were detected. Yu and Che group used
ruthenium NPs supported on hydroxyapatite to catalyze cis-hydroxilation and oxidative
cleavage of alkenes [182]. This catalyst was tested with other substrates, too, and up to 85%
yield for styrene glycol was obtained, when styrene is used. Finally, when the catalytic
oxidative cleavage of alkenes is carried out, up to 92% yield is obtained for the 1-methyl-1-
phenylethene (obtaining methylphenone). Chang group used a series of colloids to catalyze a
Heck type olefination and a Suzuki coupling [183]. When the catalyst obtained was tested in
the Heck olefination, up to 99% isolated yield, using iodobenzene and styrene. When a
commercial available Ru/Al2O3 catalyst was tested for the Heck type and Suzuki catalysis,
even better results were found.
Rhodium catalysis. By far, the most common reaction catalyzed by metallic rhodium
nanoparticles is the hydrogenation of unsaturated bonds. On the reduction of aromatic rings,
Launay’s group have carried out catalytic test over styrene, anisole, toluene, m-xylene, and
tetralin with a Rh(0) catalyst [184]. The best results are obtained for ethylbenzene from
styrene and methoxycyclohexane from anisole with almost 100% yields. Previously, the
synthesis of an other Rh(0) catalyst containing a mesoporous siliceous material, with MCM-
41 pore architecture, has been reported by the same group [185]. The resulting supported NPs
have been used in the reduction of styrene, o-, m- and p-xylene, and phenol; obtaining
ethylcyclohexane, 1,2-dimethylcyclohexane, 1,3- dimethylcyclohexane, 1,4-
dimethylcyclohexane (with a cis- preference in every case) and cyclohexanol/cyclohexanone,
respectively. A complete conversion has been reached in all cases under H2 1MPa in less than
3 h. Other silica-supported Rh(0) NPs have been achieved by Mévellec et. al. [186] During
the catalytic tests, they use a series of activated aryl rings, and the best results were obtained
for anisole and phenol (with 129 h-1TOFs) and styrene (127 h-1 TOF). The worst result was
for Aniline (31 h-1 TOF). Barthe’s group has carried out catalytic hydrogenations in toluene,
anisole and o-xilene, using silica supported metallic Rh(0) NPs [187]. The authors, changed a
series of variables and determined the best conditions, obtaining 100% conversion for toluene
and anisole, with 282 h-1 and 300 h-1 TOFS, respectively; and 94% with a TOF of 120 h-1 for
o-xilene. Besides, they found and interesting cis-/trans- 92/8 ratio of the product 1,2-
dimethylcyclohexane. Rossi’s group has achieved recoverable catalyst by synthesizing Rh(0)
NPs deposited over an amino modified silica-coated Fe3O4 system [188]. They carry out
experiments in cyclohexene and benzene obtaining >99% conversion under all conditions and
TOFs up to 7600 h-1 with cyclohexene. Carbon supported Rh(0) NPs are also used as catalyst
for aryl hydrogenation. Ikeda and co-workers have achieved a Rh(0) carbon core-shell
nanostructure [189]. t-butylbenzene was employed as model reaction obtaining 99% yield in
2 h, at 353 K. Other hydrogenations catalysis have been carried out over benzoic acid, 3-
hydrooxypyridine and byphenyl, with 85% yield for cyclohexanecarboxylic acid, 98% for 3-
hydroxypiperidine, and up to 97% for bycyclohexane. Son’s group has achieved charcoal
supported Rh(0) NPs with well defined shapes [190]. The best activities are reported for
tetrahedral nanoparticles over anthracene, with up to 99.3% selectivity for 1,2,3,4,5,6,7,8-

octahydroanthracene. Other arenes have been used in hydrogenation with these NPs; TOFs of
600 h-1 have been achieved for benzene, toluene, and methyl benzoate. Among the
nanostructured carbon supports, CNT are widely used in the production of metallic NPs.
Recently, Wai’s group has reported an investigation in the synthesis of a series of multiwalled
carbon nanotubes (MWCNT) supported nanoparticles [191]. One of them refers to a system
of metallic Rh obtained via water-in-hexane microemulsion method and then supported over
carboxylic acid functionalized nanotubes. Benzene was used as model reaction catalysis;
118.1 h-1 TOF has been achieved. In a previous article, this group used the same catalyst to
hydrogenate anthracene [192]; where 76.2% conversion has been found with a 62.4%
selectivity for 1,2,3,4-tetrahydroanthracene. In other investigation, Kakade et. al. have used
MWCNT as support materials for Rh(0) prepared by a simple microwave treatment [193].
When toluene was used for catalytic test, TON up to 9900 with nearly 100% conversion to
methyl cyclohexane has been fulfilled. Other aryl derivatives have been used to test the
catalytical activity. Wai’s group has obtained Rh(0) NPs synthesized in a water-in-CO2
microemulsion in presence of surfactants [194]. These NPs have been used in the
hydrogenation of naphthalene and phenol in supercritical CO2. In the first case, tetralin with a
>96% yield has been achieved; when it comes to phenol, >92% of conversion to
cyclohexanone and cyclohexane with a ratio 15:1, calculated from the NMR peaks intensities,
have been fulfilled. Recently, a Rh/Al2O3 catalyst synthetized by flame spray have been
accomplished by Hoxha et. al. and used in enantioselective hydrogenations tests [195]. The
hydrogenation of a couple of α-ketoesters, ethyl pyruvate and ethyl 3-methyl-2-oxobutyrate
in the presence of quinine (QN) and cinchonidine (CD), respectively, have been achieved.
The systems have shown 53% enantiomeric excess (ee) for the α-hydroxiester with 56% yield
in 2h and 59% ee with 100% yield, each. Other γ-Al2O3 supported Rh(0) NPs obtained by
Metal Vapor Synthesis have been used to hydrogenate unsatured bonds by Petrici’s [196] and
Vitulli’s group [197]. The hydrogenation of 4-(6’-methoxy-2,-naphthyl)-3-buten-2-one and 2-
acetyl-5,8-dimethoxy-3,4-dihydronaphthalene have been performed with a modified
supported Rh-trioctylamine (TOA); 100% and 86% selectivity, respectively, to the
hydrogenation of the α,β-unsatured bond have been achieved (not the carbonyl or the
aromatic fragments). In other work, the same catalyst has been used in the hydrogenation of
methylbenzoate and cinnamaldehyde, and silylformylation of 1-hexyne. In the hydrogenation
case, 80% and 100% selectivity for the α,β-unsatured bond or the aryl system have been
obtained. In the silylformylation case, a quantitative reaction and 100% selectivity for the (Z)-
1-(Dimethylphenylsilyl)-2-formyl-1-hexene product have been accomplished. By their side,
Park et. al. performed hydrogenations over anisole and benzene with a rhodium in aluminum
oxyhydroxide [Rh/AlO(OH)] prepared through a sol-gel reduction [198]. The reactions were
carried out at room temperature and 75ºC in n-hexane and solventless, respectively. They
have achieved nearly quantitative reactions in every case and TOFs up to 1700h-1. In a
previous work from the same group, the actual catalyst was entrapped in a bohemite matrix
by gelation with water [199]. The same systems in solventless conditions achieved 1000 h-1
and 5000 h-1, respectively. On the other hand, dos Santos and Dupont´s group has combined
IL (1-n-butyl-3 methylimidazolium tetrafluoroborate) and sol-gel method to immobilize
Rh(0) NPs within a silica network [200]. They have obtained TOFs up to 54 min-1 in 22 min
for 1-Decene. Other catalyst, synthesized by Cimpeanu exploits the generation and
entrampment of Rh(0) NPs in simple solid ammonium salts by inducing their supercritic CO2
melting to form ionic liquids, and has been used in the hydrogenation of cyclohexene and
benzene [201]. TOF values for both hydrogenations have been found in the order of 104 h-1
and 102 h-1, each. When it comes to colloidal catalysts, ionic liquids are commonly used as
stabilizers of many metallic NPs. Recently, Janiak group has obtained Rh(0) NPs stabilized
by ionic liquids (BMim+BF-4, BMim+OTf- and BtMA+NTf-2 [BMim+ = n-butyl-methyl-
imidazolium, BtMA+ = n-butyl-tri methyl-ammonium, OTf- = -O3SCF3, NTf-2 = -
N(O2SCF3)2]) through thermal decomposition of Rh6(CO)16 [202]. The tests were performed
in cyclohexene and yields up to 98% are obtained in 2.5 h, 75ºC, and 1% metal wt. Dupont’s
group synthesized metallic Rh(0) NPs in 1-nbutyl-3-methylimidazolium hexafluorophosphate
ionic liquid ([BMI][PF6]) under H2 at 4 bar and 75ºC for 1 h [203]. A series of hydrogenation
catalytic tests were executed to correlate the results to the Raft equation. In a previous work,
this group used the same method to carry out the hydrogenation of benzene [204]. The tests
were performed in three systems: BMI⋅PF6; acetone and solventless. The best results have
been found for the solventless conditions with 21 h-1 TOF. The authors, reported poor
conversions in many hours due to aggregations and lost of catalytic activities of the Rh(0)
NPs. Dyson’s group combined the PVP-Ionic liquid method to synthesize a catalyst highly
active under biphasic hydrogenation of unsatured molecules [205]. They compared the
catalytic activity of the Rh(0) NPs in different ionic liquids using styrene hydrogenation as
model reaction, finding better catalytic activities for ionic liquids with hydroxyl groups and
weakly- or non-coordinating anions. Nearly quantitative conversions for styrene,
cyclopentene, 1-octyne and 1-decyne, and average turnover frequency (TOF) of at least 2000
h-1 are obtained. In a similar strategy, Kou’s group used poly[(N-Vinyl-2-pyrrolidone)-co-(1-
vinyl-3-alkylimidazolium chloride)] copolymer to stabilize metallic rhodium NPs reduced
with H2 in 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid ([BMIM][BF4]) [206].
A series of substituted aryl rings were used for the catalytic tests. The best results obtained
were for benzene with 96% conversion and for phenol with a better TOF (247 h-1); although
poor conversion and a 74/26 ratio for the products cyclohexanol/cyclohexanone were
achieved. In a previous article, this group reported the catalytic hydrogenation in benzene
with the same NPs system [207]. In this study, TOF of 250 h-1 was obtained in 16 h. Diferent
bipyridine ligands were used alongside ionic liquids to obtain colloidal Rhodium NPs and
later used in aromatic hydrogenation, by Roucox and co-workers [208]. With 3,3’-bipyridine
and 4,4’-bipyridine system, 100% conversion to ethylcyclohexane has been achieved. Other
aryl derivatives used were; benzene, toluene, ethylbenzene, propylbenzene, cumene, and
styrene. The best results were achieved for 4,4’-bipyridine in all cases. Other work from this
group reports the synthesis of the same system with 2,2’-bipyridine ligand and their use in
hydrogenation of styrene under different conditions [209]. PVP is other capping agent used in
the stabilization of colloidal NPs. Delmas et. al. have used PVP protected rhodium NPs,
synthesized through a solvolysis method, to study the catalytic hydrogenation of oct-1-ene in
a biphasic system [210]. They carried out kinetic studies in the temperature range 303-323 K.
The rate was found to be first order with catalyst concentration, hydrogen pressure and oct-1-
ene concentration. Other biphasic system (water-benzene), using PVP entrapped Rh(0) NPs
reduced by Cp2V, is employed by Pellegatta and collaborators [211]. For the hydrogenation
of benzene, 250 h-1 TOF is achieved; benzene, deuterated benzene, phenylacetylene and
styrene kinetic tests were carried out also with this system. Before their silica supported
catalyst investigations, Roucoux’s group developed a series of catalytic hydrogenations with
metallic rhodium nanoparticles synthesized via chemical reduction with sodium borohydride,
and stabilized only with N,N-dimethyl-N-cetyl-N-(2-hydroxiethyl)ammonium salts
(HEA16X, X=Br, Cl, I, CH3SO3, BF4). In their last article, this group has obtained excellent
results in a one pot hydrogenation-dehalogenation of chlorobenzenes [212]. When
chlorobenzene and 4-chlorotoluene were used in the catalytic tests, 100% conversion has
been achieved to cyclohexane and methylcyclohexane in 1.7 and 7.3, respectively. Other
report, explores the hydrogenation of N-, O-, and S-heterocycles, as pyridine, 2-picoline,
quinoline, N-methylindole, furan, benzofuran, and 1,3,5-triazine [213]. In each case, a
quantitative reduction has been found, with better TOFs for furan to THF (200 h-1) and 1,3,5-
triazine (176 h-1). When thiophene and benzothiophene were used, no hydrogenation was
fulfilled. In a previous work, the influence of the counter-ion in the surfactants, over catalytic
hydrogenation of various benzene derivatives were investigated [214]. Better results were
found when HEA16Cl was employed as stabilizer; and when this catalyst was used over
disubstitued benzene derivatives, the cis- diastereomers are the major products (up to 99%).
Aditionally, they realized catalytic studies in a biphasic system [215]. With appropriate
conditions the authors, obtained TOFs of 429 h-1, 256 h-1, and 149 h-1 for anisole, toluene and
p-xilene, respectively. Other reactions catalyzed by metallic rhodium NPs less reported
include; hydrogenolysis or alcanolysis of different molecules and CO hydrogenation. Alemán-
Vázquez and collaborators have used alumina supported Rh NPs in the catalytic ring opening
of cyclohexane [216]. The best results were obtained with an impregnation route, with a 37%
conversion in 4 h. CeO2 supported Rh(0) NPs are used in the catalytic ring opening of
methylcyclobutane and hydrogenation of CO by Hayek’s group [217]. For catalytic ring
opening of methylcyclobutane, 5 h-1 – 10 h-1 TOfs were detected; for CO hydrogenation, 0.55
h-1 TOF was detected, in contrast to Rh/SiO2 were 0,15 h-1 TOF was achieved. In a previous
work, the same group used this catalyst to hydrogenate CO [218]. The catalysis for the
inverse CeO2/Rh thin film with a TOF of 4.70x10-2 s-1. Fukuoka et. al. achieved nanoparticles
inside FSM-16 siliceous material by impregnation of the Rh salt, calcination under O2, and
subsequent reduction in H2 [219]. This supported catalyst was used in the catalytic
hydrogenolysis of butane and a TOF of 195h-1 has been achieved with 96% selectivity to the
production of methane; 3% and 2% production of n-propane and ethane, respectively, is
found. An interesting catalyst chemically reduced in presence of (R)-2,2_-bis-
(diphenylphosphino)-1,1_-binaphthyl ((R)-BINAP) ligand and tetraoctylammonium bromide
(TOAB), and later supported on silica by impregnation was achieved Li’s group [220]. These
NPs were tested in the catalytic hydroformylation of styrene and vinyl acetate with a syngas
flow. When compared to unsupported Rh-BINAP, homogeneous catalyst and Rh/SiO2; 92%
branched selectivity and 25% ee (S-enantiomer) are achieved for the Rh-BINAP catalysts and
89% to 92% branched selectivity and 26% to 30% ee (S-enantiomer) for the Rh-BINAP/SiO2.
Although, low total conversion are obtained, 5% and 6-9%, respectively. Other Rh(0) NPs
used in the catalytic hydroformylation of styrene are the ones synthesized by Axet and co-
workers [221]. They have obtained colloidal NPs via H2 decomposition of two organometallic
precursors ([Rh(η3-C3H5)3] and [Rh(μ-OMe)(cod)]2) in the presence of two chiral diphophite
ligands. Regioselectivity up to >99% for the branched product with 40% of ee has been
fulfilled. In the same line of catalytic tests, Tuchbreiter et. al. obtained poly(ethylene imine)
amides (PEI) protected Rh(0) NPs [222]. The chemical reduced nanocomposite achieved
>99% conversion with 88% selectivity for hydroformylation reaction. As the Rh/PEI
prepared via H2 reduction showed better results, an experiment varying syngas pressure was
realized, where the authors found better selectivity for hydroformylation catalysis at higher
pressures; although the system was not sensitive to this variable. In a previous reaction,
Dupont group applied their Rh(0) NPs synthezised via imidazolium ionic liquids to
hydroformylate 1-alkenes [223]. Quantitative conversions to aldehydes in 4 h were found,
with 25 ratio of lineal/branched aldehydes. A catalytic related reaction is the hydrosilylation
of multiple bonds. Thiot and co-workers used a polyionic gels method to synthesize Rh(0)
NPs and used these composites in the catalytic hydrosilylation of acetylene [224]. The
reaction proceeded with regio- and stereoselectivities to afford the (E)-1-silyl-1-alkene in
89% yield. Other investigation to hydrosilylate aromatic nitriles was carried out by Petrici’s
group [225]. They used γ-Al2O3 supported and unsupported Rh(0) NPs synthesized via Metal
Vapour Synthesis (MVS). The catalytic tests were realized under solventless condition and
activated and deactivated aryl niriles were tested. Quantitative conversions were obtained for
the unsupported nanoparticles at 100ºC with trimethylhydrosylane (HSiMe3), regardless the
nitrile nature; when triethoxyhydrosylane is employed, lower conversions (75-80%) are
achieved. The supported nanoparticles denoted sensitivity to the aryl nitrile subtitution; better
conversions (80%) are obtained for benzonitrile and trimethylhydrosylane, the lower ones
were achieved for the deactivated aryl nitrile. In a later paper, this group reported a catalytic
sylilformylation reaction, adding trioctylamine (TOA), as stabilizer, to their catalyst. The
authors report tests of a reaction in 1-hexyne, and obtained a quantitative conversion in 10 h
with a 100% stereoselectivity for the (Z)-1-(Dimethylphenylsilyl)-2-formyl-1-hexene product.
Longer time reactions are required to achieve the same results when the TOA unprotected
catalyst is used. In other proceses, catalytic oxidation of molecules is also applied to metallic
rhodium NPs. Although less information about this reaction is available. In a recent
investigation, Somorjai’s group has reported studies of CO oxidation over rhodium NPs
supported on SBA-15 [226]. Better oxidations were found for smaller NPs, with up to 1.69 s-1
TOFs. When the catalysts were calcined before use, a decrease in the turnover frequency is
registered due to the formation of Rh2O3. In other report, Newton et. al. realized studies of
CO oxidation using a γ–Al2O3 supported rhodium catalyst [227]; where they found a
correlation between the catalyst performance and the existence of different Rh(0), Rh(I), and
Rh(III) phases. In the catalytic oxidation of alcohols, Hasik and co-workers carried out tests
with composites of Rh(0) and polypyrrole (PPy) [228]. When the catalysis was carried out
over isopropyl alcohol, acetone and propene were found as products in a 97.49/2.51 ratio at
370 K, 94.8/5.15 at 400 K, and 90.64/9.36 at 430 K. Acetone was also the main product, with
a lesser degree of propionaldehyde and COx, when Senkan group used a Rh/TiO2 catalyst to
fulfill the partial oxidation of propylene [229]. The titania supported NPs were obtained
through lasser ablation. Montini et. al. achieved a Rh/CexZr1-xO2-Al2O3 composite and used it
for the ethanol steam reforming [230]. The system favors the dehydrogenation of ethanol to
acetaldehyde, although some acetone formation is detected. In other work, a Rh/Ce0.2Zr0.8O2-
Al2O3 catalyst was synthesized by the same method [231]. In this work, the authors
determined that above 750 K the decomposition ethanol to H2, CO, and CO2 occurs; a clear
indication that above that temperature, the water gas shift reaction is operative.
Palladium catalysis. When it comes to palladium catalysis, many articles have been
published in the last ten years, and it is impossible review all these investigations. But two
main catalytic reactions have been reported for palladium(0) NPs: reduction of alkenes and
alkynes and C-C cross coupling. In the last case, a number of excelent reviews have been
published in the last years like Astruc´s [232-233], who focuses mainly in the catalytic Heck
cross coupling. Trzeciak published a fine review, where the author studied mechanistically
the Heck reaction [234]. On the other hand, Jones´s group reviewed palladium catalysts used
in the Mizoroki-Heck and Sukuki-Miyaura couplings [235]. Previous to these reviews, Farina
has realized a study of high-turnover catalysts, homogeneous and heterogeneous, used in
cross coupling reactions [236]. Gomez et. al. made a review where informed about C-C cross
coupling and hydrogenation reactions catalyzed by palladium NPs [237-238]. A review of
great interest in our group is the one realized by Jesús and collaborators [239]. This report
exhibits catalytic reactions carried out with dendrimer-supported palladium NPs, the type of
investigation developed by our group [240]. Hydrogenation reactions. Harada et. al. used
carbon black (CB), activated carbon (AC), and mesoporous carbon (CMK-3) to support
palladium(0) nanoparticles, and used them in the oxidation of benzyl alcohol and C=C
hydrogenation of cinnamaldehyde [241]. For the oxidation of benzyl alcohol to benzaldehyde,
the maximum activity (>80%) was achieved in an hour, when CMK-3 and AC were used with
a [NaOH]/[PdII] ratio of 4:1, and CB with a 8:1 [NaOH]/[PdII] ratio. When a commercial c-
Pd/C was tested for this catalytic reaction, the catalysts prepared by the authors showed better
activities in the 2-10 range of [NaOH]/[PdII] ratios. In the catalytic hydrogenation of
cinnamaldehyde to 3-phenylpropionaldehyde, quantitative conversion was fulfilled when
Pd/CB was used with a 4:1 [NaOH]/[PdII] ratio, in 3 h. Mastalir group has achieved
palladium(0) NPs encapsulated in graphite and used them to catalyze the hydrogenation of 1-
butene, cis-2-pentene, and cyclohexene, and isomerization of 1-butene and cis-2-pentene
[242]. When the 1-butene is tested, a quantitative conversion is achieved, with 0.086 s-1 TOF,
1.680 hydrogenation/isomerization selectivity, and 0.327 production selectivity of cis-2-
butene/trans-2-butene in the isomerization catalysis. For the conversion of cis-2-pentene, up
to 50% was achieved, in 90 minutes, with predominance for the catalytic isomerization, with
a 60% production for the trans-2-pentene, ≈5% for 1-pentene, and ≈35% for pentane. Finally,
no transformation was detected for cyclohexene. CNT are used as supports to synthesize
palladium(0) NPs. Tessonnier group used MWCNTs supported palladium(0) NPs for the
selective hydrogenation of cinnamaldehyde into hydrocinnamaldehyde [243]. Quantitative
conversions were achieved in 25 h, with 80% selectivity for the hydrocinnamaldehyde. Chun
et. al. used ionic liquid modified MWCNTs to obtain palladium catalysts and test them in the
hydrogenation of different olefins [244]. TOFs up to 2820 h-1 are achieved when styrene is
used as substrate. In a related investigation, sepiolite clay is modified with 1,1,3,3
tetramethylguanidine trifluoroacetic acid (TMG+ TFA-), 1,1,3,3-tetramethylguanidine lactic
acid (TMG+ LA-) and 1,1,3,3-tetramethylguanidine acetic acid (TMG+ AA-) ionic liquids to
support palladium(0) NPs, and use them in the reduction of alkenes and in the C-C cross
coupling [245]. The catalyst was synthesized by mixing an aqueous solution of H2PdCl4 and
the previously modified sepiolite, dried, and reduced under H2 flow. TOF up to 10000 h-1 is
achieved with quantitative conversions, when 1-hexene and styrene are employed as
substrates. The use of other ILs did not change the activity. Kiwi-Minster group explored the
ionic liquid-carbon nanofibers (CNF) anchored to sintered metal fibers (SMF) stabilization of
palladium NPs for a posterior use in the partial hydrogenation of acetylene under continuous-
flow conditions [246]. Selectivity up to 85% for ethylene was achieved with a rate of 3.7x10-2
mol(gPdS)-1, at 150º C. Hou and co-workers used the 2,3-dimethyl1-[3-N,N-bis(2-
pyridyl)propylamido] imidazolium ([BMMDPA][PF6]) and 1-n-butyl-2,3-
dimethylimidazolium hexaflourophosphate ([BMMIM][PF6]) ionic liquids to synthesize some
palladium(0) NPs via H2 flow [247]. Quantitative conversions were found when this NPs
were tested in the catalytic hydrogenation of cyclohexene to cyclohexane, styrene to

ethylbenzene, and ethyl actylate to ethyl propionate at 35º C, with a 500:1 substrate/Pd ratio.
No byproducts were detected in any case. Dupont’s group stabilized palladium(0) NPs in 1-n-
butyl-3-methylimidazolium hexafluorophosphate (BMI·PF6) or tetrafluoroborate (BMI·BF4),
via H2 reduction of Pd(acac)2 dissolved in the before mentioned ionic liquids [248]. When
these dispersions are used in the partial hydrogenation of 1,3-butadiene, 99% conversion is
achieved, with 72% selectivity for 1-butene. Crooks and collaborators are one of the first
groups in achieving dendrimer-encapsulated NPs, especially palladium and platinum
nanoparticles obtained via chemical reduction with NaBH4 of a palladium salt [249]. Part of
their investigation has focused in the correlation between the generation of the dendrimer
used to encapsulate and the activity in different catalytic reactions. In one investigation, this
group tested dendrimer-encapsulated palladium(0) NPs in the catalytic reduction of allyl
alcohols [250-251]. They have found selectivity for lineal substrates, especially with high
generation dendrimers. This behavior is attributed to steric interaction between the substrates
and the functional groups on the dendrimer periphery. Astruc group has achieved palladium
NPs stabilized by “click” ferrocenyl dendrimers catalytically active in the hydrogenation of
styrene [252]. In other investigation, this group used a series of dendrimers (triazolyl
dendrimers, triaziolylferrocenyl dendrimers, and a PAMAM dendrimer) to encapsulate or
stabilize Pd(0) NPs and used the composites to reduce styrene to ethyl benzene [253]. The
best catalytic results that they obtained for a triazolyl dendrimer first generation with 27
dendronic-9-propyl units with up to 3390 h-1 TOF when methanol was used as reducing
agent. Also, triazolyl dendrimer-encapsulated Pd(0) NPs were tested in the catalytic
hydrogenation of allyl alcohols by Astruc group [254]. When a zero generation was used,
better catalytic activities were found (8088 h-1 TOF), for the hydrogenation of allyl alcohols.
Okitsu et. al. employed a sonochemical preparation to produce Al2O3 supported NPs. The
sonochemical reduction was carried out in the presence of alcohol additives (methanol,
ethanol, and 1-propanol). When these nanoparticles were tested in the catalytic hydrogenation
of 1-hexene and trans-3-hexene, rate up to 700 mmol·(Pd-g)-1·min-1, for the hydrogenation of
1-hexene, with NPs reduced in 1-propanol. Bruening and co-workers synthesized α-Al2O3
supported poly(acrylic acid) (PAA) and polyethyleneimine (PEI) thin films. These films are
used as supports for metallic palladium nanoparticles [255]. TOF up to 3500 h-1 was achieved
in the catalytic hydrogenation of 1-propen-3-ol. In a recent investigation, the catalytic
reaction is tested when the catalyst loading is varied [256]. The best results were obtained
with lower loadings. Metallic palladium NPs embedded in a PAA and/or PEI thin film, all
supported onto alumina, were used by this group in the hydrogenation of allyl alcohols [257].
TOF up to 5880 h-1 was achieved for allyl alcohol. In a previous work from this group, the
same catalyst was used in the hydrogenation of allyl alcohols [258], and TOFs up to 727 h-1
for penten-3-ol. Ebert and co-workers obtained catalytically active poly(amideimide)
nanofibre mat supported palladium(0) NPs for the hydrogenation of methyl-cis-9-
octadecenoate (methyl oleate) [259]. When the catalytic tests were carried out, two possible
products can be detected: the trans-isomer methyl-trans-9-octadecenoate (methyl elaidate)
and the hydrogenation product methyl-cis-9-octadecanoate (methyl stereate). After their
experiments, they conclude that the process of hydrogenation of the methyl oleate takes place
via isomerization reaction. Erman and collaborators, synthesized poly(acryonitrile-co-acrylic
acid) supported NPs by electrospinning the copolymer-Pd solution [260]. The Pd reduction
was carried out by an hydrazine solution, before and after electrospinning. This catalyst was
tested in the selective hydrogenation of dehydrolinalool (3,7-dimethyloct-6-ene-1-yne-3-ol,

DHL), up to 11.3 reaction rate is achieved when the catalyst is synthesized when a high
concentration of acrylic acid co-polymer was used and the reduction was carried out after
electrospinning. Somboonthanakij and collaborators, have synthesized SiO2 supported
palladium(0) NPs, via flame spray pyrolysis method, with palladium acetylacetonate and
tetraethylorthosilicate (TEOS) as palladium and silicon precursors, to use them in the partial
hydrogenation of 1-heptyne [261]. TOF up to 66.2 s-1 has been achieved, with 42%
conversion and 93% selectivity for the 1-heptene product. In a recent investigation, this group
used the same catalyst in the same reaction to compare its performance with an impregnation
made catalyst. Up to 95% selectivity for 1-heptene is achieved, with a 75% conversion, when
10% loading of flame spray made catalyst is used. Obare’s group used a series of supported
and unsupported Pd(0) NPs to catalytically hydrogenate styrene, 1,5cyclooctadiene, and 6-
bromo-1-hexene [262]. The n-dodecyl sulfide stabilized NPs were achieved by reducing with
hydrazine hydrate and sodium hydroxide in presence of n-dodecyl sulfide, using ethanol as
solvent. In other experiment, these NPs were supported over silica. The best conversions were
obtained for the silica supported NPs, with quantitative conversions in the reaction of styrene
to ethylbenzene; the same results were found for the reaction of 6-bromo-1-hexene to 1-
bromohexane; in the hydrogenation of 1,5-cyclooctadiene, quantitative conversion was found,
although a 1:1 ratio is achieved in the production of 1-cyclooctene and cyclooctane.
Jayaraman’s group modified silica with poly(ether imine) based dendritic phosphine ligands
to support palladium(0) NPs [263]. When this catalyst was used in the hydrogenation of
various olefins, quantitative reactions were obtained in each case, in 4 h or less, at 25º C. on
the other hand, Mastalir et. al. tested MCM-41 supported palladium(0) NPs and tested in the
hydrogenation of alkyne reductions [264]. The catalysts were obtained by hydrazine
reduction, before and after addition of SiO2 precursor (Na2Si3O7), using
tetradecyltrimethylammonium (C14TABr). TOF up to 5.56 s-1 with 8.7% conversion was
achieved in the case of 1-hexyne with 100% selectivity to 1-hexene. A similar result was
reached for the conversion of 3-hexyne (5.34 s-1) with 8.2% conversion and 94.5% selectivity
to the trans-3-hexene product. Better results were achieved by Minsker group in the selective
reduction of 1-hexyne to 1-hexene (9.2 s-1, in 85% conversion with 96.5 selectivity) [265]. In
a recent experiment, this group achieved shape defined palladium NPs, by NaBH4 or ascorbid
acid reduction of H2PdCl4 in presence of cetyltrimethylammonium bromide (CTAB) [266].
These NPs were used in the catalytic hydrogenation of 2-methyl-3-butyn-2-ol. The best
results were achieved with the largest Pd spheres. In a previous article, the group used
PdCl2(NH3)4 as metal precursor, and used the NPs in the same catalytic reaction [267]. Other
report from this group sinthezised palladium(0) NPs stabilized in block-copolymer micelles
and used them in the selective hydrogenation of 2-butyn-1,4-diol [268]. TOF up to 0.91 s-1
was achieved when the alumina supported catalyst was used, 94% selectivity is reached in a
quantitative reaction. A gel type resin (FCN) as a result of copolymerization of glycidyl
methacrylate (GMA), styrene, and ethylene glycol dimethacrylate, was used to support
palladium NPs, and test them in the hydrogenation of 2-butyne-1,4-diol and phenylacetylene
[269]. For the hydrogenation of 2-butyne-1,4-diol, up to 92% selectivity for the 2-butene-1,4-
diol product was obtained with a total of 90% conversion, although from this product, up to
50% suffers other processes like isomerization, decomposition, etc. In the reduction of
phenylacetylene to styrene, the catalyst yielded 90% of total conversion, with up to 91.4%
selectivity to styrene. An increase in the palladium loading did not increase the rate of
hydrogenation or the selectivity. Nanospheres derived from hydroxylated polyisoprene (PHI),

cross-linked poly(2-cinnamoyloxyethyl methacrylated) (PCEMA), and poly(acrylic acid)
(PAA), were developed by Underhill et. al. to encapsulate palladium(0) NPs and test them in
the catalytic reduction of triethylallyl ammonium bromide (TEAA), vinylacetic acid (VAA),
methyl methacrylate (MMA) and ethylene glycol dimethacrylate (EGDMA) [270]. The
catalysis was improved when the tests were carried out at a pH=10. When it comes to
colloidal systems, surfactants like cetyltrimethylammonium bromide (CTAB) were used to
stabilize palladium(0) NPs. Piccolo and co-workers used this cationic surfactant to produce
well defined palladium NPs in dispersion [271]. The best results were found when prism-like
NPs were used in the catalytic reduction of 1,3-butadiene (0.80 s-1 TOF). A colloidal system
of palladium(0) NPs were obtained by Wai and collaborators to hydrogenate 1-phenyl-1-
cyclohexene, methyl trans-cinnamate and trans-stilbene [272]. When this catalysis was tested
in 10-(3-propenyl)anthracene, >50% conversions were detected after 9 minutes of reaction.
This group combined H2SO4-HNO3 modified MWCNTs and supercritical conditions to
support Pd(0) NPs [273]. The palladium reduction was carried out in supercritical CO2, with a
H2 flow, in presence of the nanotubes. This catalyst was used in the hydrogenation of trans-
stilbene; 96% conversion is achieved in 10 min of reaction. In other investigation, the group
used high density polyethylene (HDPE) granules and fluoropolymer (PFA) tube to support
Pd(0) NPs [274]. The deposition was the same, and quantitative monoreduction of
naphthalene was achieved in 10 minutes with the HDPE supported Pd(0) NPs. Lower but
good conversions were carried out in benzene and phenol in 60-50 minutes. In a previous
work, this group used a water-in-CO2 microemulsion to obtain palladium NPs and use them
in the reduction of a number of olefins [275]. In the catalytic hydrogenation of 4-
methoxycinnamic acid, trans-stilbene, maleic acid and nitrobenzene >99% conversion were
detected in almost each case (>95% conversion for styrene) in 20 s to 30 min (for the
reduction of nitrobenzene to aniline). By their way, Lee and co-workers used a supercritical
CO2 system to synthesize mesoporous silica SBA-15 supported Pd(0) NPs to hydrogenate the
4-methoxycinnamic acid benzyl ester [276]. The catalyst was prepared by mixing
palladium(II) hexfluoroacetylacetonate (Pd(hfac)2) with SBA-15 in THF, drying, and later
loading the palladium(II) composite into a reactor and producing the super critic CO2.
Quantitative conversion was achieved when 150 bar of CO2 was added to the hydrogenation
reaction, with a 93% selectivity for the ester product. Meric et. al. also used a super critical
CO2 to synthesize Pd(0) NPs, which were used in the catalytic hydrogenation of citral [277].
When the catalysis was carried out in super critic conditions; >99% conversion was achieved
in less than an hour, with up to 68% selectivity for the citronellal (CIAL) product. Other work
from this group reports the same catalytic system [278]. Sastry and collaborators obtained a
H-Y zeolite grafted with amine groups to support Pd(0) NPs [279]. When tested in the
hydrogenation of styrene, penylacetylene, and nitrobenzene, quantitative reactions were
achieved in 30 min, 90 min, and 40 min, respectively, with 99.2%, 85.9%, and 100%
selectivity for ethylbenzene, ethylbenzene, and aniline, each.
Silver catalysis. The main catalytic reaction reported with metallic silver nanoparticles is
the reduction of nitrogen compunds. Recently, Liu et. al, have immobilized PVP supported
silver NPs onto halloysite nanotubes through reduction of AgNO3 by polyol process [280].
This composite was used in the reduction of 4-nitrophenol to 4-aminophenol; kinetic studies
were carried out to determine the effect concentration of NaBH4. Murugadoss and co-workers
embedded silver NPs inside a chitosan matrix [281]. Obtaining a TOF value of 1.5x10-3 s-1.
Qian group carried out a similar investigation [282]. They have supported the silver NPs over
a cuttlebone derived organic matrix (β-chitin) by reducing via Tollen’s reagent and NaBH4.
At 10 min, they have achieved a 71.5% conversion. By their side, Pradhan et. al. achieved
colloidal silver NPs reduced with NaBH4, CO, N2H4, and ascorbic acid [283]. Faster results
were found with the NaBH4 reduced NPs. In a related catalytic reaction, Rupa and
collaborators have used TiO2 supported NPs to photodegradate the commercial dye Reactive
Yellow-17 (RY-17) [284]. More investigations have been developed in the degradation of
commercial dyes, like the one realized by Demir group, who used microfiber supported silver
NPs to reduce methylene blue [285]. This nanocomposite, along with NaBH4, reached a total
degradation within 11 min; although they do not report which products were obtained. An
experiment was carried out in the absence of the silver NPs, and no degradation was
observed. In a previous work, Kundu and co-workers used this catalytic reaction to sense low
concentrations of ammonia in solution [286]. Other catalytic degradation carried out by
metallic silver nanoparticles is the phenol degradation. Dai’s group supported silver NPs over
TiO2 with a twistlike helix structure [287]. They report better photocatalytic results with the
NPs obtained via chemical reduction. Again, they didn’t report any possible product in the
reaction. Other group of reactions commonly catalyzed by metallic silver NPs is the oxidation
of molecules. Li and collaborators obtained silver NPs with well-defined shapes and used
them to oxidize styrene to benzaldehyde and styrene oxide [288]. The truncated triangular
silver NPs were synthesized by a solvothermal method in N,N-dimethylformamide (DMF) in
the presence of PVP. The best catalytici results were obtained with cubic NPs in 12 h with
82% conversion. A 81:19 ratio for benzaldehyde was achieved. Debecker and co-workers
obtained silver NPs via multiple layers surfactants and latter supported over TiO2 or
V2O5/TiO2 by wet impregnation, and used them in benzene oxidation to CO2 and H2O [289].
The Ag-V2O5/TiO2 showed better conversion (100%) at 350ºC than the Ag-TiO2. In a recent
investigation, Tian and collaborators obtained Ag/SBA-15 catalysts prepared through an in
situ reduction method using hexamethylenetetramine (HMTA) and formaldehyde as reducing
agents and used them in the catalytic oxidation of CO [290]. When the formaldehyde reduced
catalyst was tested in the CO oxidation, no catalytic activity was detected below 150ºC and its
maximum activity (100% conversion) was detected at 270ºC; while the HMTA reduced
catalyst showed low activity at temperatures slightly above room temperature, although its
catalytic maximum (100%) was reached at 230ºC. In a slightly different reaction, Kaneda’s
group has explored the catalytic oxidation of phenylsilanes to silanols [291]. Their catalyst
are hydroxyapatite (Hap) supported silver NPs. When dimethylphenylsilane was used, 99%
conversion was obtained, with a 99:1 selectivity for dimethylphenylsilanol; different
phenylsilanes were used, and conversions of 96% - 99% were achieved in each case. In
contrast, when tris n-butylsylane and t-butyldimethylsilane were tested, no catalytic activity
was found.
Osmium. The reports on osmium metal nanoparticles have been focused on the synthesis,
thus Wang et. al. [292] obtained an average particle size of the Os nanoclusters in a stable
colloidal solution of 0.9 nm with a size distribution of 0.6 – 1.8 nm (σ:0.28). The Os
nanoclusters can be separated from the reaction system as a precipitate and the precipitated
can easily ‘‘dissolve’’ in many organic solvent such as acetone and THF to form stable
colloidal solutions. Gyenge et. al. [293] used tetrabutylammoniumtriethylhydroborate
(C4H9)4N[BH(C2H5)3] as both reductant and stabilizer, obtaining a mean particle size of 2.4
nm. Os NPs are electrochemically active for BH4- oxidation. Yung and coworkers [294] have
synthesized Os NPs supported on MWCNTs by vacuum pyrolysis at 573 K using
[Os3CO10(NCMe)2] as precursor. The NPs prepared have a mean diameter of 1.8 nm.
Osmium islands deposited on Pt (111) have been synthesized by Strbac et. al. [295] and
Pacheco Santos et. al. [296], using this system for the catalytic oxidation of ethanol.
Iridium. Dupont et. al. [297] have realized several studies about synthesis of
nanoparticles in different ionic liquids(ILs); where, their results indicate that IL reacts with
the nanoparticle surface and generate surface-bound protective species which on the one
hand, is responsible to some extend for their catalytic activity, but on the other hand, explains
their relatively low stability that leads to aggregation/agglomeration and eventually to the
bulk metal. Reduction of [(1,5-COD)IrCl]2 by H2 in neat acetone yields 1 equivalent of H+Cl-
for each Ir(I) reduced to iridium(0) resulting in a highly efficient (100%), acid-assisted, high
selectivity(100%) acetone hydrogenation catalyst [298]. Mévellec et. al. [299] have obtained
aqueous suspensions of Ir NPs through chemical reduction of IrCl3 assisted by sonication in
the presence of a surfactant: N,N-dimethyl-N-cetyl-N-(2-hydroxyethyl)ammonium chloride
salt. This catalytic suspension was efficient for hydrogenation of benzenederivatives such as
mono or disubstituted arenes and provides the corresponding saturated compounds. Due to
the reaction is carried out in two phases; catalyst can be reused after simple decantation in a
separating funnel without a significant loss of activity. Yinghuai et. al. [300] have obtained
iridium NPs using a different ionic liquid as stabilizer. Ir nanoparticles (~3.5 nm) are used for
borylation of benzene and catalyst is recyclable by extraction of impurities. Stowell et. al.
[301] have synthesized iridium NPs in the presence of different capping ligands to
hydrogenate 1-decene to decane. They found that “good” capping ligands appear to be poor
choices for catalytic applications. So, the ligands must be strong enough binders to stabilize
nanocrystals but weak enough to provide reactant access to the metal surface. Rodríguez-
Gattorno et. al. [302] have prepared iridium NPs supported on Al2O3. This catalyst was used
for opening the cyclohexane ring showing better results than Rh/Al2O3. Cunha and Cruz [303]
reported decreased activity for very small metal particles (1-2 nm) in the study of the
hydrogenation of benzene and toluene over Ir /γ-Al2O3. Yang et. al. [304] have obtained Ir
NPs supported on SiO2 using cinchona alkaloids and (1S,2S)-diphenylethylenediamine as
chiral modifier to improve the dispersion and stability of the Ir particles. A good catalytic
performance in the asymmetric hydrogenation of acetophenone in MeOH was obtained.
Catalyst can be recycled by centrifugation-decantation method. Gupta et. al. [305] have used
presynthesized iridium nanocrystals stabilized by weakly bound tetraoctylammonium
bromide (TOAB) ligands to be infused into presynthesized mesoporous silica using CO2 and
toluene to produce an active catalyst for 1-decene hydrogenation, where desorption of ligands
from the adsorbed nanoparticle surface, onto the support and into the decene during reaction,
will enhance metal binding to the surface and aid catalyst stability. Miyao et. al. [306] have
used a reversed micelle technique to obtain hollow silica nanospheres (~35 nm) containing Ir
NPs (1-2 nm) for studies in hydrogen storage. Park et. al. [307] have reported the synthesis of
iridium NPs in aluminum oxyhydoxide Ir/AlO(OH). This catalyst was proved to be active for
hydrogenation of various arenes and ketones under mild conditions, room temperature and
even with an hydrogen balloon. Catalyst was recupered by simple filtration. Iridium-based
films on Au electrode surface have been synthesized by Birss et. al. [308], sol-gel solution
showed Ir NPs of 1-2 nm average size and IrOx were not detected.
Platinum. Yang et. al. [309] have obtained platinum NPs stabilized by polyaryl ether
trisacetic acid ammonium chloride dendrimer through an alcohol reduction method. Such
nanoparticles are used to carry out hydrogenation of nitrobenzene derivatives with molecular
hydrogen under mild conditions. The catalytic activity of the dendritic catalyst decreased with
the increase of the generation of the dendrimer, this can be explained considering that larger
dendrimers could limit the accessibility of the substrates into the active centers of platinum
nanoparticle-cored dendrimer. Using other dendrimers as stabilizers for Pt NPs, Du et. al.
[310] have carry out the hydrogenation of phenyl aldehydes to phenyl alcohol under an
atmospheric pressure of H2. Huang, et. al. [311] have synthesized platinum NPs stabilized
with a PAMAM G4OH dendrimer, then NPs were immobilized onto mesoporous silica SBA-
15. Ethylene and pyrrole hydrogenation reactions were studied, and it was found that the
activity was increased to a certain temperature. This behavior is explained by a partial
decomposition of dendrimer capping. In the same way, Deutsch et. al. [312] have used
hydroxyl terminated PAMAM G4 dendrimers to stabilize platinum NPs obtained by reduction
of Pt2+ with hydrogen. After, silica was added to a Pt-G4OH. In order to “activate“ the
catalyst, the dendrimer was removed via calcination. Lang et. al. [313] have used PAMAM
G5 OH dendrimers to obtain stabilized platinum NPs that were deposited on SiO2. After
removal dendrimer, toluene hydrogenation and CO oxidation were studied. Esumi et. al.
[314] have used poly(propyleneimine) (PPI) dendrimers and PAMAM dendrimers to stabilize
platinum NPs. They found that the average particle sizes of the metal nanoparticles are almost
independent of the concentration of the dendrimer as well as the generation for both the
PAMAM and the PPI dendrimers. The nanocomposites were used for reduce 4-nitrophenol to
4-aminophenol, the rate constants decrease with increasing dendrimer concentration. This
decrease is attributed to the increase of the dendrimer adsorption on the metal nanoparticles.
Michels et. al. [315] have obtained platinum NPs stabilized by supramolecular dendritic
assemblies of β-cyclodextrins and PPI dendrimers, they proposed that low generation
assemblies do not provide kinetic barriers to prevent NPs aggregation into larger metal
clusters. Puniredd et. al. [316] have obtained Pt NPs within a ultrathin film matrix formed by
covalent layer-by-layer assembly of pyromellitic dianhydride (PMDA) and second generation
PAMAM dendrimer in supercritical CO2. This film matrix is immobilized onto SiO2.
Presence of nanoparticles within the dendrimer layers are important to demonstrate the charge
storage effect for non-volatile memory applications while the dendrimer layers act as a host
network to trap the Pt nanoparticles. Using a G6-OH PAMAM dendrimer, NaBH4 and
different amounts of K2PtCl4, Ye et. al. [317] have obtained platinum NPs of different sizes
and small narrow size distributions. Dendrimer encapsulated nanoparticles (DENs) are
immobilized in a glassy carbon electrode and are used for oxygen reduction reaction (ORR).
When the size of DENs was reduced, lower ORR activity was observed, also, the total Pt
surface area decreases as the sizes of the DENs decreases. Recently Knecht et. al. [318] have
reported that dendrimer complexes with Pt2+ are not fully reduced when exposed to BH4- in
aqueous solutions. Platinum NPs supported over hypercrosslinked polystyrene (HPS) have
been synthesized by Bykov and collaborators [319]. Modification of Pt/HPS catalyst with
cinchonidine gave better results for enantioselective hydrogenation of ethylpyruvate. Marty´
et. al. [320] have studied the hydrogenation of isophorone at room temperature and pressure
H2=2 bar with platinum NPs. Okamoto et. al. [321] have obtained a nanocomposite made of
MWCNTs, poly(benzimidazole) (PBI) and Pt nanoparticles. MWCNTs are wrapped with PBI
and deposition of Pt nanoparticles was carried out via polyol method. The composite was
used for methanol oxidation and have higher efficiency than carbon black/Pt system. Zhu et.
al. [322] have obtained MWCNT/PANI composite films supporting electrodeposited Pt NPs.
The composites were used for the electrochemical oxidation of formic acid. Taylor et. al.
[323] have obtained Pt/SWCNTs composite in supercritical methanol. Using a surfactant
(SDS) in the synthesis of Pt NPs they have obtained superior polymer electrolyte membrane
(PEM) fuel cell activity. Bayrakceken et. al. [324] have obtained platinum NPs supported on
the outer surface of MWCNTs by reduction of PtMe2COD using hydrogen on supercritical
CO2. Song et. al. [325] have reported that generation in situ of platinum seeds and
autocatalytic growth in presence of surfactants leads to two- and three-dimensional platinum
nanodendrites. Changing liposomes type, sheetlike nanodendrites or foamlike nanosheets of
platinum can be obtained. Luo et. al. [326] have reported crown-shaped platinum NPs using
UV irradiation in the presence of G4-NH2 PAMAM dendrimers in water. Dendrimers also
play a role as stabilizers for the particles. Platinum particles supported on polypyrrole (PPy)
and polyaniline (PANI) have been used by Hasik et. al. [327] to catalyze the isopropyl
alcohol conversion. They found that activity of PPy-based composite was higher than the
exhibited by the PANI-based one. This fact was explained by the authors by the presence of
different acidic centers in the polymers. Yoo et. al. [328] have synthesized platinum NPs
encapsulated on Al2O3, this support provides small diameter and size distribution due to its
pore dimension. Such nanostructures were used for hydrogenation of propene. Collier et. al.
[329] have prepared solvent stabilized Pt NPs by the electron beam evaporation of the metal
and co-condensation with the vapours of organic solvents at 77 K in a Torrovap metal atom
reactor. These NPs were used for the enantioselective catalytic hydrogenation of ethyl
pyruvate and shown similar results that previous supported analogous. Using a Pt/PVP
colloidal solution in methanol, 298 K and hydrogen at 0.1 MPa, Liu et. al. [330] have
achieved hydrodechlorination of monochlorobenzene to benzene and finally to cyclohexane
with high catalytic efficiency. Using Pt PVP-protected NPs as precursor Lin et. al. [331] have
obtained a Pt/PVP@MCM-41 composite (MCM-41: mobile crystalline material) which is
active in the conversion of cinnamic acid in their corresponding hydrocynnamic acid.
Platinum NPs embedded in polypyrrole(PPy) nanowires have been synthesized by Li et.al.
[332] over a glassy carbon electrode (GCE), and were used for electrocatalytic oxygen
reduction and methanol oxidation. Comparing PPy-Pt/GCE with Pt/GCE they have found that
the activity and stability of the Pt nanoclusters embedded in PPy nanowires were higher than
pure Pt deposited on electrode. Advantage of this system is attributed to a protection effect of
the 3D structure of the composite to poisoning. Synthesis of platinum-polystyrene
nanocomposite through an alcohol-reduction method has been studied by Kim et. al. [333]
this method have the advantage that do not need an additional reduction agent. Wang et. al.
[334] have synthesized platinum nanoparticles reducing H2PtCl6 with ethanol in presence of
PVP. Modifying PVP and ethanol amounts can obtain different particle sizes. Dendrimer
encapsulated platinum NPs functionalized with glutamate dehydrogenase and supported on
CNT, have been employed by Tang et. al. [335] to build a multilayer biosensor of glutamate.
Li et. al. [336] have used Octa(diacetic aminophenyl) silsesquioxanes (OAAPS)to stabilize
Pt, Pd and Ru NPs. That have been used for hydrogenation of phenyl aldehydes. Kostelansky
et. al. [337] have stabilized Pt NPs with the water-soluble phosphine ligand tris(4-
phosphonatophenyl)phosphine (TPPTP). The negatively charged TPPTP-Pt NPs were
electrostatically deposited onto a glassy carbon electrode (GCE) modified on multilayers and
are used for oxygen reduction reaction (ORR). Platinum-silica aerogel nanocomposites have
been synthesized by a supercritical impregnation method by Yoda and collaborators [338].
Niesz et. al. [339] have obtained Pt NPs by reduction of H2PtCl6 in water with NaBH4 in the
presence of the capping poly(ethylene oxide)13-poly(propylene oxide)30-poly(ethylene
oxide)13 triblock copolymer at room temperature. Addition of anionic Pt salt under flowing H2
gave larger NPs. Mark et. al. [340] have proposed the use of S layers from S. acidocaldarius
and D. radiodurans as a biomolecular template to order arrays of dendrimer encapsulated
platinum NPs. This approached, provide regular 2D arrays. Park et. al. [341] have obtained a
Pt/PPy nanocomposite by means of ultrasonic irradiation in the presence of sodium dodecyl
sulfate or poly(N-vynil-2-pyrrolidone).
Gold. There are numerous routes for the production of colloidal Au(0) nanoparticles, but
the method described by Brust and its variation are one of the most popular synthetic schemes
in the field [342]. Gold nanoparticles functionalized with carbohydrates (glyconanoparticles)
have been synthesized by several groups [343]. Tang et. al. [344] have found that large citrate
protected gold nanoparticles (around 17 nm) can be extracted from water into chloroform
using hyperbranched polyethylenimine (HPEI) polymers, and hyperbranched polymer
showed better results than its corresponding linear analog. Pérignon et. al. [345] have
mentioned that synthesis of dendrimers is prohibitive for many applications because of the
high cost of the dendrimer synthesis although hyperbranched polymers can be easily
accessible and they can effectively stabilize metal nanoparticles in organic solvents. Using a
hyperbranched polymer chemically analogous to PAMAM dendrimers, they have obtained
gold nanoparticles. Kumar et. al. [346] have synthesized gold NPs in the matrix of a
plasticized anion-exchange membrane, where gold NPs are dispersed throughout the matrix
of the membrane but excluded from the surface. Wu and coworkers [347] have developed a
method in which nanocomposite with hydrophilic clay faces and hydrophobic polystyrene
(PS) brushes in the edges are used to stabilize PS colloidal particles, after poly(2-vinyl
pyridine) (P2VP) chains are adsorbed to the surface of these particles and then gold NPs are
prepared in P2VP brushes. Ishida et.al. [348] have deposited gold NPs onto polymer beds
such as poly(methyl methacrylate) (PMMA), polystyrene (PS), polyaniline (PANI),
poly(vynilchloride) (PVC) and melamine-formaldehyde resin (MF). Catalytic performance of
Au/polymers over oxidation of glucose with H2O2 was affected by the kinds of polymer
supports and has less influence by the size of Au nanoparticles. PMMA as polymeric support
of gold NPs have been used by Kuroda et. al. [349] for studying the reduction of 4-
nitrophenol to 4-aminophenol and it was compared with other reported supports for the same
reaction.The results indicate that the structures of polymer supports play an important role in
determining the catalytic activities. Oxidation of 1-phenylethanol with dioxygen in water
catalyzed by microgel-stabilised gold NPs with poor results, have been developed by Biffis
et. al. [350] They argue that the bad performance of the Au nanoclusters may be partially
related to their large size. However, Miyamura et. al. [351] have obtained better results not
only with 1-phenylethanol but with several alcohols at room temperature under atmospheric
conditions. These results were obtained using gold nanoclusters stabilized with polystyrene.
Using a four dendritic thiol ligands, Advincula [352] have found that average size of gold
NPs increases while the sizes distributions becomes broader as the size of thiophene dendron
increases. They argue that the increased steric congestion, between dendrons, leads to slower
reaction with the growing Au nanoparticles, resulting in the formation of larger gold clusters
and broader size distribution. One-dimensional arrays of Au-dendrimer nanocomposites have
been obtained by Torigoe et. al. [353] using poly(oxymethylphenylene) dendrons (PPD) of
generations (G) 1-4 functionalized with a thiol group at the focal point as capping ligands.
The size and shape of Au-NCDs (nanoparticles-cored dendrimers) change with the generation
number of dendrons [354]. When increasing the generation number of dendrimer the size of
the gold nanoparticles increases and polydispersities too. Gold nanoclusters capped by
dendron thiol-terminated Fréchet-type benzyl ether dendrons (G1) have been synthesized by
Li et. al. [355] Size-controlled gold nanoparticles were obtained by the variation of the mole
ratio of G1 to Au. The Au atoms in the G1-gold clusters were largely Au(0). Love et. al.
[356] have determined that using branched ligands leads to smaller and better defined Au NPs
than using an analogous nondendritic stabilizer, indicating that also, the structural nature of
the dendritic branching must play a role in controlling nanoparticle growth - not just the
simple steric effect of dendritic ‘size.’ Shon et. al. [357] have obtained nanoparticle-cored
dendrimers (NCDs) through the synthesis of monolayer-protected nanoparticles and then
adding dendrons on functionalized nanoparticles by a coupling reaction. Tomalia and Huang
[358] have reported Cystamine core (G1–3) PAMAM dendrimers reduced to their respective
thiol core, functionalized dendrons using DTT. Bakshi et. al. [359] have obtained gold NPs in
aqueous phase in the presence of sodium dodecylsulfate (SDS) and
dodecyltrimethylammonium bromide (DTAB) and poly(amidoamine) dendrimers (PAMAM).
Krasteva and coworkers [360] have found that resistivity and vapor-sensing properties of
chemiresistors made from gold nanoparticle/poly(propyleneimine) composite films depend on
the size (generation) of the dendrimers. Using maltose-modified PPI dendrimers (generation
2-5), Pietsch and collaborators [361] have obtained gold NPs using NaBH4 or only dendrimer
as reducing agent. For the 4th generation dendrimer (G4) the autoreduction process is much
faster compared to the low generation dendrimers G2 and G3, in the case of G5 dendrimer,
the reduction of metal ions is practically instantaneous. Lee et. al. [362] have reported,
through a one pot synthesis, a composite made of SWNT-PANI-Au; polymerization of aniline
and formation of Au nanoparticles (average size 5 nm) are simultaneously achieved in the
presence of γ-irradiation. Using a two-phase method Rodríguez-Vázquez et. al. [363] have
obtained gold clusters capped with tetrahexylammonium bromide. These clusters are stable in
aqueous solution for several years. In order to functionalize gold NPs, a poly(aryl ester)
dendron was used by Frein et. al. [364] They have obtained NPs in biphasic media using
tetraoctylammonium bromide (TOAB), water, toluene and NaBH4 obtaining nanoparticles
ordered in evenly spaced rows. The separation between the rows corresponds to 1.3 times the
length of the dendron in its fully extended conformation. The average size of the
nanoparticles was 1.2 ± 0.4nm. Huang et. al. [365] have obtained gold nanorods via oxidation
of spherical gold nanoparticles using NaH2PO4 in the medium of cetyltrimethylammonium
bromide (CTAB). Fabrication of hydrophobic gold nanorods from hydrophilic one have been
developed by Mitamura et. al. [366] DNA-based gold nanostructures have been synthesized
by several groups obtaining bi- and tridimensional arrays [367]. Olefin metathesis can be
achieved on the surface of gold nanoparticles [368]. Gold NPs supported over TiO2, CeO2,
Al2O3 and SiO2 have been used by Zanella and collaborators [369] for the water gas shift
reaction. Again, it is mentioned that nature of the support must be taken into account in order
to explain the catalytic behavior of these catalysts. Mertens et. al. [370] have studied the
catalytic oxidation of several 1,2-diols to α–hydroxy-carboxylates with gold nanocolloids

They argue that in comparison with Pt and Pd, Au is more resistant to deactivation by
chemical poisoning or overoxidation and it displays a higher intrinsic chemoselectivity. Au
sols were prepared by reduction of HAuCl4 with NaBH4 in an aqueous solution of
poly(vinylalcohol), obtaining gold NPs with average size of 2-4 nm, this catalyst was
recovered by filtration through a membrane (polyimide, cellulose acetate,
poly(dimethylsiloxane) or DESAL-5 DK) and then reutilized without significant lose of
activity. Gazsi et. al. [371] have studied the synthesis of hydrogen via methanol oxidation
using gold supported on CeO2, Al2O3, TiO2, MgO, activated carbon and SiO2. Dapurkar et. al.
[372] have used gold NPs (less than 10 nm) supported on TiO2, MgO, Al2O3, CeO2 and C for
studying the oxidation of benzylic compounds into their corresponding ketones without
solvent at 1 O2 atm and T ≤ 100°C. Mitsudome et. al. [373] have reported that the oxidative
lactonization of diols using molecular oxygen as a primary oxidant can be catalyzed by
Hydrotalcite supported gold NPs. Guan et. al. [374] have studied the ethanol dehydrogenation
by gold nanoparticles supported on mesoporous sillicas and conventional sillicas obtaining
different particle sizes. Maximum activity for alcohol dehydrogenation was observed at a
particle size around 6 nm. Methanol oxidation over Au/TiO2 (prepared by deposition
precipitation method) catalyst have been studied by Nuhu et. al. [375]. Supported gold
chloride is the most active catalyst for the hydrochlorination of ethyne, the activity being
correlated with the metal's high standard electrode potential was reviewed by Bond and
Thompson [376]. Diao et. al. [377] have reported that gold submicroparticles (AuSMPs)
dispersed on indium tin oxide (ITO) are catalytically active toward CO electrooxidation in
solution. They also found that the halide ions (Cl-, Br-, I-) exhibit significant poisoning effect
on the catalytic activity of AuSMPs/ITO electrodes. Oxidation of nitic oxide can be catalyzed
by TiO2-Au nanocomposite film electrode as reported by Milsom et. al. [378]. Films have 30-
50 nm per layer and gold NPs exhibit a 20 nm average diameter. Santosh et. al. [379] have
prepared a catalyst of MWNT, polyaniline (PANI) and gold nanoparticles (8-10 nm) MWNT-
PANI-Au, which was used to demonstrate electrocatalytic oxidation of methanol and CO.
Gold NPs supported on TiO2 were used by Raptis et. al. [380] as a heterogeneous catalyst for
the isomerization of epoxides to allylic alcohols in high yields and good selectivity. Au over
SiO2, TiO2 and silylated materials have been synthesized by Aprile et. al. [381] and used for
epoxidation of alkenes with O2, they demonstrate that intermediates of reaction involves
organo-gold species.
CONCLUDING REMARKS AND FUTURE PROSPECTS

As matrices, supports, templates or protectors, polymers that are part of the composites
help nanoparticles to work better as catalysts by lowering costs, by increasing their selectivity
and/or reactivity, by being environmentally friendly or through a combination of these
applications. Thus, the study of this kind of materials is still growing and, providing a new
twist on Feynman's famous quote, it is necessary to keep in mind that there is plenty of
room, not only at the bottom, but everywhere in order to find the “dream catalyst”, the best
catalyst which is cheap, recoverable, recyclable, efficient and non-contaminant. Thus, as
mentioned above, there is a promising future and still a lot of work to be done to get the best
catalyst ever designed.
288 Rocío Redónn, N. G. Garcíía-Peña and F. Ramírez-Creescencio
ACKNO
OWLEDGME
ENTS
Financial support
s for thhis research by PAPIIT IN101308
I andd PUNTA is gratefully
accknowledgeed.
ABOUT THE AUTH

HORS
Rocío Reddón was born in Mexico City C in 1969. In 1993 she obtained herr B. Sc. In
Chemistry at thhe Universidaad Nacional Autónoma
C A de México. Obtaaining her Phh. D. in the
saame Universitty in 2002. During
D her Ph.. D. studies, she
s had the oportunity
o of working
w in
diifferent Chemmistry Groups aroun the Woorld; in 1997 in i England in Essex Univerrsity and in
19998 in Oxforrd University with Prof. J. R. Dilworthh; in 1998 inn Spain, with Prof. Ana
A
Albeniz at Valladolid Univeersity, and in USA
U at Hawaaii University with Prof. Crraig Jensen
frrom 1998 to 2001. Finallyy she obtainedd a Post-docttoral position in the “Labooratorio de
M
Materiales y Nanotecnologíaa, CCADET” in the Universsidad Nacionaal Autónoma de d México,
w
where she actuaally works on the synthesis and characterrization of nannocomposites dendrimer-
nooble metal NPPs and their caatalytic applicaations.
M
Metallic Nanopparticles Nanocomposites 29
Nidia G. García
G Peña was
w born in Toluca,
T Mexico, in 1982. She obtainedd her B.Sc.
deegree in chem
mistry from thhe Universidaad Nacional Autónoma
A de México in 20008. She is
cuurrently workiing with Prof. Redón in nannostructured materials
m appliied to catalysis, to obtain
heer M.Sc. degreee in chemistrry. She expects to graduate in
i 2010.
Fermín Raamírez was born in Pueblaa, México, inn 1984 and studied s chemistry at the
U
Universidad Nacional Autónnoma de Méxxico. His unddergraduate reesearch was done d in the
grroup of Prof. Rocío
R Redón concerning frree-solvent synnthesis of iriddium nanopartiicles. He is
cuurrently comppleting his Maaster thesis on interactions of
o iridium nannoparticles witth dendritic
sppecies.
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Chapter 2
RECENT EVOLUTION OF OXIDATION CATALYSIS

BY MO COMPLEXES
Carla D. Nunes* and Pedro D. Vaz

Centro de Química e Bioquímica, Departamento de Química e Bioquímica
Faculdade de Ciências da Universidade de Lisboa
Ed. C8, Campo Grande, P-1749-016 Lisboa, Portugal
ABSTRACT
For 80% of all compounds produced in chemical and pharmaceutical industry at least
one catalytic step is essential during their synthesis. Catalysts speed up chemical
reactions but can be recovered unchanged at the end of the reaction. They can also direct
the reaction towards a specific product and allow reactions to be carried out at lower
temperatures and pressures with higher selectivity towards the desired product. This is a
principle that is pursued with increasing emphasis and dedication leading to far more
specific and cleaner processes.
Homogeneous catalysts, on the other hand are usually complexes, which consist of a
metal centre surrounded by a set of organic ligands. The latter impart solubility and
stability to the metal complex and can be used to tune the selectivity of a particular
catalyst towards the synthesis of a particular desirable product. By varying size, shape
and electronic properties of the ligands, the active site at which the substrate binds can be
constrained in such a way that only one of a large number of possible products can be
produced. Oxidation catalysis is a quite important transformation in both industrial and
academic aspects. Within this field, catalysts, ranging from a variety of available metal
centered systems, which rely on Mo are one of the most important.
Traditionally, oxidation catalysts are based on metal oxides, holding M=O moieties,
with the metal center lying in high oxidation state. A large number of important chemical
reactions are catalyzed by MoVI complexes. Inclusively, several industrial processes such
as ammoxidation of propene to acrylonitrile, olefin epoxidation (ARCO and Halcon
processes), and olefin metathesis reactions are carried out over molybdenum catalysts.
Furthermore, as molybdenum is highly available to biological systems, the coordination
*
Corresponding author: Phone: +351 217 500 876, Fax: +351 217 500 088, E-mail: cmnunes@fc.ul.pt
44 Carla D. Nunes and Pedro D. Vaz
chemistry of MoVI has stimulated considerable interest in view of its biochemical

relevance, and many MoVI complexes have been studied as models of molybdoenzymes.
In recent years the development of new approaches to prepare new and stable
catalyst has turned to low oxidation state MoII organometallic complexes. These pre-
catalysts proved to be quite adequate to the purpose by being highly active and selective
in the epoxidation of olefins and in oxidation of other substrates. Additionally, such pre-
catalyst complexes are more stable towards air and moisture which allows easier
handling.
This chapter lights up some recent advances on olefin oxidation chemistry based on
Mo catalysts with special focus on the development of new approaches to achieve active
catalysts.
INTRODUCTION
The significant enzymatic role of molybdenum in biochemical reactions [1–3] specially
in the oxidation of aldehydes, purines and sulfides [4] induced chemists to use molybdenum
complexes as biomimetic catalysts in the oxygenation of organic compounds [5,6]. Under
such auspices, MoVI dioxo-complexes have been extremely investigated [7–9] particularly
with respect to the catalytic role of transferase enzymes like nitrate reductase in which their
active sites consist of a cis molybdenum dioxo moiety [10,11]. The ability of molybdenum to
form stable complexes with oxygen-, nitrogen-, and sulfur-containing ligands led to
development of molybdenum Schiff base complexes which are efficient catalysts in both
homogeneous and heterogeneous reactions [12–15]. The activity of such complexes varies
markedly with the type of ligands and coordination sites [16].
Molybdenum-catalyzed olefin epoxidation has received interest from both academic and
industrial research laboratories because epoxides are important building blocks in organic
synthesis and polymer science [17–20]. Although numerous procedures have been developed
[21-24], there is still a need for the development of new catalysts that may uncover a more
detailed understanding of oxidation pathways and inform the design of more efficient
catalytic systems. Since the first example of a molybdenum oxo complex catalyzing the
epoxidation of alkenes with peroxides such as organic hydroperoxides and hydrogen peroxide
[25], a variety of different complexes have been developed [26–41].
Despite this, molybdenum catalysts are also suitable for many other oxidation reaction
types. Oxidation of alcohols to aldehydes and ketones is one of the most important
transformations in organic synthesis [42–44]. In particular, the oxidation of primary alcohols
to aldehydes is important since they find wide applications as intermediates in fine chemicals
particularly for perfume industry [45–48]. Traditionally, the oxidation of alcohols is carried
out using stoichiometric inorganic oxidants such as permanganate, bromate, or chromate
based reagents which generates large amount of heavy metal waste [49-52]. Several transition
metal-based homogeneous systems such as palladium [53–64], ruthenium [65–68],
manganese [69,70], tungsten [71], rhenium [72], copper [73,74], and iron [75,76] have also
been reported. However, mixtures of the organic substrates, products, solvents, and molecular
oxygen are well known for being explosion hazards in many cases. In addition, catalytic
oxidation of amines is also a major functional transformation in organic synthesis [42–46].
Amongst the possible amine oxidation products (hydroxyl, nitroso, nitro, azo and azoxy),
aromatic nitroso compounds are utilized extensively as chemical feedstocks for a wide range
Recent Evolution of Oxidation Catalysis by Mo Complexes 45
of useful materials such as dyes, pharmaceuticals, perfumes and plastics [47,48]. As a

drawback, amine oxidation poses problems due to non-regioselectivity or over-oxidation of
amines and competitive oxidation of substrates.
Within this context, MoVI complexes have proved also as adequate catalysts for such
transformations being explored in several works given its functional as well as structural
similarity with molybdo-enzymes catalyzing a variety of oxidation reactions [77–80].
Oxidation reactions using Mo complexes occur in the presence of terminal oxidants,
Chart 1, such as hydrogen peroxide (H2O2), or organic hydroperoxides, such as urea hydrogen
peroxide complex, tert-butyl hydroperoxide, ethylbenzene hydroperoxide, cumyl
hydroperoxide and trityl hydroperoxide.
Chart 1
Hydrogen tert-Butyl
Urea·H2O2 complex 2
peroxide 1 hydroperoxide 3
Ethylbenzene Cumyl Trityl

hydroperoxide 4 hydroperoxide 5 hydroperoxide 6
From this library of peroxide oxidants it has been found in recent years that H2O2 is the
least competent oxidation agent concerning olefin epoxidation. In this way olefin epoxidation
reactions have centered mainly on the use of the organic hydroperoxides. When these are
used, olefin epoxidation proceeds via a Lewis acid catalyzed process. This is a class of
reactions known as heterolytic reactions involving a two-electron transfer process. In this
process the catalytic center does not undergo a change in its oxidation state. It occurs since
the electron-transfer steps involving the metal are concerted and accordingly there is no
valence net change in the metal. The key role of the metal is then to activate the organic
peroxide (ROOH) in such a way that an O atom from it may be transferred to the olefin.
OXIDATIONS WITH [MOVIO2]2+ COMPLEXES AS CATALYSTS

The majority of studies dealing with catalytic applications using high-oxidation state
VI
Mo complexes has traditionally relied on the use of simple complexes centered on the
tetrahedral MoO2X2 (X = Cl, Br) core shown in Chart 2.
Chart 2
7, 8
Particular interest in MoVI-oxo complexes arose in the late 1960s when ARCO and
Halcon presented patents on the olefin epoxidation catalyzed by MoVI compounds in
homogeneous phase [81,82]. In the following years different mechanisms were suggested to
explain the reactivity of these complexes. The debate as to which of the two main proposed
mechanisms is more accurate, the one favored by Mimoun et al. [83] or the one suggested by
Sharpless et al. [84] has not been settled to date, despite the fact that several theoretical and
mechanistic studies have been presented [85]. It has been generally agreed, however, that
formation of a MoVI alkyl peroxide occurs followed by transfer of the distal oxygen atom of
the alkyl peroxide rather than an oxo ligand [86]. The industrial ARCO and Halcon process
employs tert-butyl hydroperoxide (tbhp) as oxidizing agent. Despite the fact that H2O2 is a
more environmentally friendly oxidant (the only byproduct formed is H2O), tbhp has other
advantages that still make it the preferred oxidizing agent in industrial processes [87].
A kinetic model, proposed by the groups of Kühn and Gonçalves [88], was built up for a
homogeneous batch reactor based on a simplified mechanism involving three steps: (i)
reversible coordination of tbhp to the starting MoVI complex to give a MoVI alkylperoxide; (ii)
irreversible oxidation of cyclooctene to cyclooctene oxide by the species formed in step 1,
with formation of the starting complex and tert-butyl alcohol; (iii) reversible coordination of
tert-butyl alcohol to the starting complex. This model is consistent with the observed kinetics.
The first step in this reaction mechanism was characterized in more detail by studying the
kinetics of the reaction of the starting complexes with tbhp in the absence of any reductant by
UV/Vis spectroscopy. Rate constants, equilibrium constants, and activation parameters were
determined. All ΔS‡ values were negative and therefore support an associative mechanism in
which a seven-coordinate intermediate is formed. The results also suggest that the first step is
not always the rate-limiting step of cyclooctene epoxidation with these complexes. DFT
calculations later on have confirmed such findings for such mechanism proposal [89]. This
mechanism, proceeds through coordination of the hydroperoxide to the metal center, Scheme
1. Coordination proceeds by means of the distal oxygen atom of the peroxide, rather than the
proximal one. The very next step is the H-atom transfer to one of the oxo ligands of the metal
center.
It then starts with a hydrogen transfer from the peroxide to one of the terminal Mo=O
oxygen atoms and the remaining t-BuOO− anion binds as a seventh ligand, forming a five-
membered ring held together by a hydrogen bond. In the second step, a concerted approach of
the olefin to the Mo–Od (Od = distal) bond gives rise to an intermediate containing a seven-
membered Mo–C–C–Od–Op(t-Bu)···H–O–Mo ring (Op = proximal). In the final step,
decomposition of the intermediate leads to the starting complex, alcohol and the desired
epoxide. The activation energy for the addition of the olefin (second step) is the highest one,
in agreement with available kinetic studies showing that the catalyst formation is not always a
rate-limiting step. There is also evidence that the resulting alcohol by-product (t-BuOH) can
react with the starting complex, competing with t-BuOOH and hence leading to the
progressive catalyst poisoning, which has been observed experimentally.
Scheme 1. Proposed reaction mechanism for t-BuOOH activation and olefin epoxidation at the NOX
face of octahedral [Mo2O2X2L2] (X = Cl, Br, Me) complexes. The metal is hidden for clarity. Op and Od
stand for proximal and distal O atoms in peroxide.
From the continuing research developed using such catalysts, much of the work has
centered on ligand design. Many works have been devoted to exploring the chemistry of a
large family of complexes of formula MoO2X2(N,N’) or MoO2(N,O)2 where N,N’ and N,O
are bidentate ligands and X = Cl, Br, alkyl [89–101]. The reactivity and selectivity of such
complexes is largely dictated by the bidentate ligands and recently a high asymmetric
induction was achieved for the first time on this kind of systems [102]. The simpler MoO2X2
or MoO2X2L2 derivatives (L = labile ligand) have been less studied in this regard [103–105].
Starting from the late 70’s and early 80’s decades of the XXth century, a rising interest in
stable organometallic complexes arose during the development of models for reactive
intermediates for the nitrogenase enzyme [106–108]. For this reason, reactions of
MoO2X2(bpy) (X = Cl, Br ; bpy = 2,2’-bipyridine) precursors with different Grignard
reagents were thoroughly explored by Schrauzer and co-workers. The first isolated
compounds were of the type MoO2BrR(bpy) and being synthesized by reacting MoO2Br2
(bpy) with different organomagnesium halides in thf. Some of the MoO2BrR(bpy) complexes
were isolated [R = Me [106], Et [106], CH=CH2 [107]], while others were only generated in
solution [R = Pr, i-Pr, t-Bu, CH2C(CH3)3] [108]. Complexes with Me and Et react back with
Br2 to yield MoO2Br2(bpy) and CH3Br or C2H5Br, respectively.
A modification of the synthetic method used for MoO2BrR(bpy) afforded the preparation
of several complexes of composition MoO2R2(bpy), as evidenced in Chart 3.
Chart 3
The first compound of this type obtained, MoO2Me2(bpy) [109], was synthesized by
reacting MoO2Br2(bpy) with methylmagnesium chloride in thf. Several other complexes,
namely, ethyl [112], propyl [112], butyl [112], neopentyl [110], cyclopentyl [112], cyclohexyl
[112], benzyl [111], several aryl [113–116], and organosilicon derivatives [117], followed in
the following years using different Grignard reagents. From this set of complexes,
MoO2Me2(bpy) exhibits a high thermal stability (melting point = 503 K) and is stable under
air. The decomposition temperatures were found to be related to the stability of the Mo-C
bond. Decomposition was observed to occur on prolonged heating under basic or acidic
conditions in solution. The most temperature sensitive are those complexes with hydrogens in
β-position like the diethyl derivative or those where steric effects cause an additional Mo-C
bond labilization, as found in the c-C6H11 derivative.
In 1991 the first examples of MoO2R2L2 complexes were reported, where L2 was not bpy
but 4,4’-dimethyl-2,2’-dipyridyl (Me2-bpy), conferring a higher solubility to the synthesized
compounds [118]. The MoVI compounds MoO2R2L2 [L2 = Me2–bpy; R = CH2–CHMe2 (9),
CH2–CMe3 (10), (CH2)4CH=CH2 (11), CH2Ph (12), CH2C6H4Me-p (13), and CH2CMe2Ph
(14), Chart 4, were prepared by reaction of the corresponding Grignard reagents with
MoO2Br2L2, followed by aerobic oxidation of the resulting reaction mixture.
Chart 4
9
12
10 13
11
14
The decomposition reactions of these compounds were studied in very detail by Vetter
and Sen [118]. The complexes were found to decompose in solution under inert gas
atmosphere at varying rates. The course or rates of the reaction were found not to be
influenced by the nature of the solvent in use. As the decomposition evolves, insoluble
molybdenum oxides are formed and in solution quantitative amounts of hydrocarbons can
also be detected. Anaerobic decomposition associated with a given complex is a sensitive
function of the hydrocarbyl group R. If β-hydrogens are present on R, equal amounts of
alkane and alkene are formed through a β-hydrogen abstraction pathway. When β-hydrogens
are absent from R, the predominant product is the free radical R· formed by Mo-R homolysis.
Other complexes of the type MoO2R2L2 (R = CH3, C2H5; L = bidentate Lewis base
ligand) were reported by the research groups of Gonçalves, Kühn, and Romão during the past
decade [34,94,95,119,120]. A wide range of compounds was synthesized, bearing a variety of
bidentate ligands of the type 1,4-diazabutadiene (R-dab), with different R groups,
phenanthroline, and substituted bypiridines, Chart 5.
Chart 5
Besides providing access to more soluble complexes, which are better amenable to
reactivity and spectroscopic characterization than the modestly soluble MoO2R2(bpy)
derivatives, the different stereochemical and electronic characteristics of these ligands impart
distinct reactivities to the MoO2R2 core. Such complexes were obtained by alkylation of
MoO2X2L2 (X = Cl, Br) with the appropriate Grignard reagent [34,94,119,120].
The catalytic properties of MoO2X2L2 (X = Cl, Br) and MoO2R2L2 [R = CH3, C2H5; L =
1,4-diazabutadiene (R-dab), with different R groups, phenanthroline, or substituted
bypiridines] (Chart 5) have been recently studied in detail by several research groups
[34,94,95,119,120]. The complexes were found to be active for the epoxidation of olefins
using tert-butylhydroperoxide as oxidant at moderate temperatures (328 K). However, when
H2O2 was employed as the oxidant, no epoxidation products could be obtained, Scheme 2.
The catalytic performance of such complexes is resumed in Table 1 showing results of
olefin epoxidation using both MoO2X2L2 (X = Cl, Br) and MoO2R2L2 (R = CH3, C2H5; L =
N,N’-bidentate ligands) complexes as catalysts.
Scheme 2. Efficient and inefficient olefin epoxidation using tbhp and H2O2, in the presence of MoVI
catalysts.
Table 1. Catalytic performances of catalysts based on MoO2X2L complexes (X = Cl, Br,

CH3; L = bidentate Lewis base ligand) in cyclooctene epoxidation at 328 K and after
24 h reaction [94].
X L Conversion %
Cl 89
15
Br 73
16
57
17
65
18
27
19
24
20
CH3 35
21
35
22
92
23
89
24
60
25
29
26
72
27
48
28
40
29
In most cases, the overall yield obtained after 4 h is relatively low (between 5 and 60%),
but increasing greatly up to 24h reaction time. However, over a 24 h period yields proved to
be strongly dependent on L and R ligand type used. Electron-attracting ligands L lead to more
active compounds, rendering the electron deficient molybdenum center. Steric effects of the
ligands also seem to play an important role on the catalytic activity. Ligands, which create
more steric hindrance near the metal center, usually decrease the catalytic performance of
complexes. Increasing both reaction time and temperature leads to a significant increase in the
product yield in all examined cases. However, at ca. 363 K further increase in product yield is
hampered by catalyst decomposition. This is most evident with the organometallic MoO2R2L2
(R = CH3, C2H5; L = N,N’-bidentate ligands) derivatives. It is also remarkable that during the
catalytic cycle loss of the R group as methane, ethane, or methanol by a potential M–C bond
breaking does not play an important role.
The use of MoO2X0-2L1,2 (X = halogen; L = mono-, bi- or tridentate ligands) complexes
have also been thoroughly studied as evidenced in Table 2. In fact variation of the
coordination sphere around the metal center (0-2 halogen ligands and 1 or 2 Lewis base
ligands) were found to be crucial based on the reported results.
From the results shown in Table 2, it is possible to observe that terminal olefins are
generally more resistance to oxidation and that the use of H2O2 does not favor the reaction.
This is quite clear in the epoxidation of cyclooctene where reactions do occur to completeness
in the presence of tbhp while with H2O2 they do not.
Table 2. Catalytic Performance of MoO2X0-2L1,2
(X = halogen; L = mono-, bi- or tridentate ligands) complexes in olefin epoxidation.
Conversion Epoxide
X L Olefin Oxidant Ref.
% sel. %
— O2 96 0 121
30
O2 86 85
O2 95 81
tbhp 73 100 122

31
tbhp 46 100
tbhp 100 100
tbhp 96 100
tbhp 70 100
tbhp 96 100
tbhp 46 65
tbhp 48 68
tbhp 40 100
tbhp 77 91
tbhp 45 100
F H2O2 99 100 123

32
Cl tbhp 100 100 124

33
tbhp 100 59
H2O2 68 100 125
34
Table 2 (Continued).
Conversion Epoxide
X L Olefin Oxidant Ref.
% sel. %
tbhp 100 100 126
35
H2O2 80 100 127
36
tbhp 96 100 128
37
Room temperature ionic liquids (RTILs) have also been used as alternative solvents. The
catalytic properties of MoO2R2(Me-p-tolyl-dab)2 (38, 39) (R = Cl, CH3 ; Me-p-tolyl-dab =
1,4-p-tolyl-1,4-diaza-2,3-dimethyl-1,3-butadiene) were assessed for olefin epoxidation under
not only the previously applied conditions (tbhp as oxidant, 328 K) but also using as
alternative solvent several RTILs, Chart 6 and Table 3 [129].
Chart 6
38, 39
The authors reported that this complex presents excellent selectivity toward the epoxide
formation relatively high activity under solventless conditions or with additional solvent,
either chlorinated or an adequate RTIL. The application of RTILs also enabled the catalyst
recycling. From several RTILs tested in recycling catalytic experiments with complex 39 the
best results were observed for the system using [bmim]NTf2, as evidenced in Table 3, entry 8.
When developing catalysts for a given reaction one must bear in mind not only high
activity but more important, selectivity. In fact if a catalytic system is not selective then it is
of no real use. In a quest for more efficient and selective catalysts some works have devoted
to the development of MoVI catalysts with chiral ligands to yield enantiopure compounds. The
need of enantiomerically pure chiral compounds faces a continuous rise. This is powered by
the increasing number of legal regulations and health concerns as well as the need for
industrial efficient processes. Enantiopure complexes are used mainly in pharmaceuticals but
not limited to, as well as in other sectors such as flavor and aroma chemicals, agricultural
chemicals, and specialty materials.
Development of chiral active pharmaceutical ingredients (APIs), in particular, is of major
relevance since it is recognized that enantiomers of a chiral compound can have dramatically
different biological activities, in some case with severe adverse effects [130]. Chiral
epoxidations are currently of high interest for the synthesis of non-racemic chiral
intermediates in the pharmaceutical and chemical industries to generate such optically pure
products [87]. Chiral epoxides, for example, are a key structural unit present in many
biologically active compounds as well as in important natural products [131]. Asymmetric
catalysis is a particularly elegant and efficient method to achieve the introduction of such
functional groups into larger organic compounds [132].
From the results discussed above in this chapter, it was shown that non-chiral MoVI
(organo)complexes could successfully yield racemic epoxides. Such results led to the belief
that some chiral derivatives of these complexes might be applied equally efficiently as chiral
catalysts. The application of chiral MoVI complexes in olefin epoxidations was a spin-off of
the application of homogeneous MoVI catalysts in the Halcon and Arco processes [81,82].
Starting in the 70’s decade of the XXth century, MoVI complexes with different types of chiral
ligands, among which diisopropyltartrates, lactamides and several other hydroxyacid amides,
have found application in chiral epoxidation reactions. Some examples accounted with the
use of N-alkyl ephedrines [133], methyl pyrolinols and diisopropyl tartrates as ligand species
[134]. Chiral ligands which were easy to make and stable in oxidation reaction conditions
were also searched for. Ligands that would also allow the possibility of varying steric
characteristics easily through simple substitutions, were found in the class of 2’-pyridyl
alcohols, which were known to be easily accessible [135,136] and from which MoO2L2 (L2 =
2’-pyridyl alcoholate) type complexes that were active as catalysts for epoxidation, could be
prepared.
Table 3. Catalytic performance of MoO2R2(Me-p-tolyl-dab)2 (R = Cl, CH3) complexes

(38, 39) for olefin epoxidation in the presence of regular solvents or RTILs [129].
R Solvent / RTIL Conversion % Epoxide sel. %

Cl None 100 100
Dichloroethane 94 100
73 100
[bmim]PF6 (R = nBu)
CH3 None 100 100
Dichloroethane 100 100
90 100
[bmim]PF6 (R = nBu)
[C8mim]PF6 (R = nOct) 94 100
96 100
[bmim]NTf2 (R = H)
[bdmim]NTf2 (R = CH3) 53 100
14 100
[C5O2mim]PF6
92 100
[(d-h)2dmg]PF6
In 1999 Bellemin-Caponnaz and others demonstrated this by applying the ligand 2-

[(−)menthol-pyridine] to such a complex [137]. A conversion of ca. 20% with an ee of 25%
using 1-hexene as substrate, was obtained. In 2000, Herrmann et al. [138] made use of chiral
precursors, Chart 7, to form enantiomerically pure 2‘-pyridinyl alcoholates which were
subsequently applied as chiral ligands in MoVI complexes.
Chart 7
40 41 42
The complexes were examined for their catalytic activity and good conversions, in the
range of 70%, being observed. Enantioselectivities were more dependent on the ligands being
found to range between 4 and 26%, with the bulkier norbornane ligands leading to the highest
optical inductions. Later on, in 2001, Gonçalves and coworkers [139] reported MoVI dioxo
complexes holding coordinated pyridyl alcoholate ligands and used in olefin epoxidation.
Mono-substituted complexes were more active than those with two chiral ligands. Another
class of suitable C2-symmetric bis(oxazolines) chiral chelating ligands were developed in
parallel [96] by Romão et al. for the epoxidation of trans-β-methylstyrene. Using tert-
butylhydroperoxide (tbhp) as oxidant at 328 K, up to 86% conversion was achieved although
ee’s were very low, lying in the range from 4 to 6%. Teruel and colleagues [92] also applied
chiral oxazoline ligands attached to MoO2 cores, Chart 8, 43. In that case the oxazoline
ligands were bound to the metal by a covalent Mo–O bond in contrast to previous reports,
Chart 8, 44 [96].
Chart 8
43 44
Using styrene as substrate, toluene as solvent and tbhp as oxidant, conversions from 25 to
30% were reached within 18 h at 308 K. Selectivity was below 50% and ee’s were still
negligible (ca. 2%). Kühn and coworkers [98] also synthesized MoO2Cl2L (L = oxime),
[MoO2(thf)2L] (L = cis-p-menthane-3,8-diol) and MoO2Cl(thf)L (L = 8-phenylthioneo- and
isoneomenthol) complexes. Conversions were found to reach 63–82% obtained with the cis-
β-methylstyrene as substrate, tbhp as oxidizing agent and toluene as solvent (328 K). The
observed ee’s were on an average low, with 24% in the best case using complex (45), Chart 9,
at 72% conversion.
Chart 9
45
The first sugar ligands were attached to [MoO2]2+ moiety by Rao and coworkers [140] in
2001, to prepare complexes of general formula MoO2L (L = sugar), Chart 10.
Chart 10
46, 47
These were applied in olefin epoxidation by Kühn et al. [141]. Turnover frequency (TOF)
was high (13000 h-1 in the best case) when cyclooctene was the substrate although velocity of
reaction slowed down with increasing time. When esterification was used to protect the –OH
group in the sugar ligand tridentate coordination of the ligand took place due to Lewis acid
catalyzed deacetylation. In the case of cis-β-methylstyrene ee’s of up to 30% were achieved.
In 2004 Herrmann published [142] further results in continuation of previous work
published in 2000 [138]. A number of chiral 2’-pyridinyl alcohols were used as ligands for
the MoO2 core. When tbhp or cumyl hydroperoxide (chp) were used as oxidants and trans-β-
methylstyrene as substrate, ee’s of up to 23% and conversions up to 58% (temperatures 323–
343 K) were reached [142]. Following also their previous work [92], Teruel et al. published
further research, in 2004, which made possible to explain the good activity and low
enantioselectivity of the MoVI complexes with coordinated oxazoline ligands [143]. They
proposed a reaction mechanism for olefin epoxidation catalyzed by a seven-coordinate
molybdenum species with hemilabile ligands as it was later on confirmed by kinetic and
theoretical studies [88,89], and already discussed in this chapter. In the same year, Singh and
coworkers [144] also reported a chiral MoVI compound with bidentate oxazoline ligands,
active in the epoxidation of styrene, reaching yields of up to 70%. Kühn et al. used a
tetradentate chiral Schiff base, see Chart 8, 44, obtaining ee’s up to 26% with cis-β-
methylstyrene [145]. Gonçalves and coworkers also prepared chiral 1,4-diazabutenes of the
type R–N=C(Ph)–C(Ph)=N–R; (1R,2R)-N,N’-dibenzylidenecyclohexane-1,2-diamine and
hexa-coordinate MoVI complexes [100]. The resulting complexes were applied as effective
catalysts for epoxidation using cis- and trans-β-methylstyrene by tert-butylchloroperoxide.
Reactions were found to proceed with high retention of configuration and high selectivity to
the epoxide, only for cis-β-methylstyrene though. In this case high 77% ee at room
temperature was obtained (at 24% conversion). Increasing the reaction temperature increased
the epoxide yields but good enantiomeric excesses (ca. 65%) could only be achieved at low
conversions (ca. 12%). Shi and coworkers [146] used both mono and tetradentate compounds
for the asymmetric olefin epoxidation of cis-1-propenylphosphonic acid with 30% aqueous
hydrogen peroxide affording (1R,2S)-(−)-(1,2)-epoxypropyl phosphonic acid. This reaction is
strongly influenced by ligands, solvents as well as reaction temperatures. For example in a
complex with a tetradentate salen ligand, Chart 11, better ee’s were obtained in
noncoordinating solvents such as methylene chloride than in a solvent like ethanol. An ee of
69% for a MoVI complex coordinated to ligand 48 was observed at 30% conversion after 24 h
reaction time.
Chart 11
48
In addition to these results, a few others not discussed within the text are screened in
Table 4, stressing the relevance and difficulties of assessing enantiopure epoxides.
In fact, the systems presented in Table 4 using the pyridine 2’-alcoholate ligands reported
by Hamann [148] were found to be quite original since they relied on the use of chiral
hydroperoxides instead of the use of chirality in the ligands. The outcome was the synthesis
of epoxides with good ee’s and additionally, these being obtained from a linear terminal
olefin which is usually seen as unactivated.
In parallel studies some attention has been devoted, in recent years, to the use of
[MoO2(acac)2] (acac = 2,4-pentanedionate) in the epoxidation of olefins as well as in sulfide
oxidation using tert-butyl hydroperoxide (tbhp), cumyl hydroperoxide (chp) or trityl
hydroperoxide (thp) and chiral bis-hydroxamic acid (bha) derivatives as ligands [149-151]. In
olefin epoxidation experiments all oxidation products were achieved in high enantiomeric
excess (ee) and, additionally it was found that an excellent regiospecificity was also achieved,
Table 5.
Table 4. Chiral epoxidation of olefins with MoO2L2 complexes and organic hydroperoxides.
Epoxide ee
Complex Olefin Oxidant Conversion % Ref.
Sel. % %
tbhp 92 100 <5 147
49
7 <5
36 <5
AcO OAc
O 100 100 50 148
OOH
50
100 100 30
100 100 20
100 100 28
100 100 53
100 100 40
100 100 38
100 100 34
From Table 5 it is possible to conclude that trisubstituted and terminal alkenes also
provided good selectivity (entries 8−13). Another important aspect of such Mo–bha catalysts
is that it selectively oxidizes the most electron rich alkene in the presence of multiple double
bonds (entries 14, 15, 17). Encouraged by the selectivity observed for myrcene oxidation
(Table 5, entry 16, squalene (Table 5, last entry), an important biogenetic precursor of
steroids and polycyclic terpenoids, was subjected to similar reaction conditions. To delight of
the authors, the Mo-bha complex in the presence of 1 equiv of chp selectively provided 2,3-
epoxysqualene with good enantioselectivity (69% ee). It was noteworthy since synthesis of
2,3-epoxysqualene often requires multiple steps.
Asymmetric sulfide oxidation, has garnered extensive attention from the synthetic
community, for the rapid preparation of enantiopure sulfoxides. Of particular value are those
compounds which contain chiral sulfoxides, a structural class widely utilized in both the
pharmaceutical industry and academia [152-156]. Although a number of methods for
assessing high enantioselectivity during sulfide oxidation have emerged in recent years [152-
165], low enantioselectivity and restrictive structural requirements are still serious obstacles
for such transformation [152-156].
The Yamamoto group has reported also the use of the Mo-bha system for asymmetric
sulfide oxidation, according to the reaction shown in Scheme 3.
Scheme 3. Reaction conditions for asymmetric sulfide oxidation using Mo-bha catalytic system.
Table 6 evidences the most relevant achievements stressing catalysts capability to

perform such transformations which are relevant in organic synthesis.
Additionally in that work [150] the authors have also reported kinetic resolution for
formation of sulfides to sulfones, as evidenced in Scheme 4.
In this way the authors have found that the Mo-bha system selectively oxidizes a single
optical isomer with resulting resolution enhancement which is sometime so difficult to
achieve [150].
In a different approach, Sheikshoaie [166] has reported selective oxidation of sulfides to
sulfoxides or sulfones by varying the quantity of urea hydroperoxide (uhp) used as oxidant, in
the presence of a MoVI dioxo complex. In this way if uhp/sulfide ratio is 1 only sulfoxides are
obtained. On the other hand if that ratio rises to 5 sulfones are selectively obtained. This is a
fine example of selectivity tuning based on variation of reaction conditions.
OXIDATIONS WITH [MOVIO(O2)2]2+ COMPLEXES AS CATALYSTS

Transition metal peroxo and peroxy complexes have played for some time now an
important role in the epoxidation of alkene substrates to their respective epoxide products. A
variety of synthesis of peroxocomplexes of various metals are known [167–169] to catalyze
the oxidation of olefins, arenes, phenols, alcohols, phosphines and sulfides [170–174].
Table 5. Chiral epoxidation of olefins using MoO2(acac)2 complex with bha ligands [149].
Ligand Olefin Oxidant Epoxide Yield % ee %
tbhp 20 28
51
tbhp 15 42
52
chp 72 66
thp 27 96
chp 82 87
53
tbhp 92 96 (R,R)
chp 77 64 (R,S)
Table 5 (Continued).
thp 95 85 (R)
chp 84 82 (R)
O
chp 95 85 (R)
tbhp 77 43 (R)
Ph
chp 89 50 (R,S)
tbhp 41 81(S,S)
tbhp 47 33 (E/Z)
chp 91 75 (R)
tbhp 13 43
chp 33 69
Table 6. Asymmetric sulfide oxidation using MoO2(acac)2 complex with bha ligands and
thp as oxidant [150].
Sulfide Reaction time / h Yield / % ee (%), config
16 81 79 (S)
20 75 81 (S)
19 76 75 (S)
18 81 82 (S)
24 66 62 (R)
17 82 86 (S)
19 83 72 (S)
O O
N N
O O O
S (PhiPr-4)3C OH OH C(4-iPrPh)3 S S
+
MoO2(acac)2 , thp, CH2Cl2
Racemic
273 K, 41 h 45 (75% ee) : 55
298 K, 24 h 46 (68% ee) : 54
Scheme 4. Kinetic resolution of sulfoxides during sulfoxide to sulfone oxidation.
The catalytic activity of peroxometal complexes is influenced by the type of metal atom,
the number of peroxo ligands attached to the catalyst and the nature of the remaining ligands
in the coordination sphere [175–187].
In this regard MoVI complexes are an important class of oxidants for this type of reaction,
and quite a number of studies have been conducted [22,27,188,189]. Similarly to that
described previously in this chapter, much of the impetus for this research has in many ways
been due to the early contributions by Mimoun et al. in 1969 [190] and the earlier
development of the Arco [81] and Halcon industrial processes [82].
In oxoperoxo chemistry of Mo, an important structural motif, in which two peroxo

groups and a doubly bonded oxo ligand create the median MoO(O2)2 plane, is well known
[191].
This core, although recognized as most stable [191] and a common motif in oxoperoxo-
molybdenum [192], has a high formation tendency, but is also a rather reactive species, which
readily performs substrate oxidation, converting itself into a [MoO(O2)]2+ core, which gives
more stable compounds than its diperoxo analogue.
In such complexes, organic ligands are generally used to complete the coordination
sphere. When these are less bulky, the 7-coordinate complexes obtained are of the type
MoO(O2)2L (L = bidentate ligand) [177,193–195]. In the case of bulkier ligands, the
oxomonoperoxo core, namely, [MoO(O2)]2+ accommodates the bidentate ligands by forming
oxomonoperoxo complexes of the type MoO(O2)L2 (L = bulky bidentate ligand) [193-195].
Recently, it has been shown that the MoO(O2)2 cores with bidentate ligands are useful
catalysts in the epoxidation of olefins [196–200].
MoVI-peroxo complexes also catalyze the oxidation of alcohols to carbonyl compounds
[201] and amides to hydroxamic acids [202,203]. In addition some other achievements in
oxidation of several organic substrates with varying functional groups, among which primary
and secondary alcohols, as well as sulfides have also been reported [204–210].
Despite enormous effort that has gone into developing these processes, far lesser progress
has been made over the years in obtaining highly stereoselective versions of this reaction
using oxoperoxo MoVI chiral complexes at either the stoichiometric or catalytic level.
The quest for a chiral analogue of the Mimoun oxodiperoxo MoVI type complexes of
general formula MoO(O2)2Ln (n = 1,2; L =H2O, dmf, hmpa, py), Chart 12, for olefin
epoxidation using molecular oxygen [190], yielding chiral epoxides, is still an open
challenge.
In the late 1970’s Schurig et al. [211] reported the preparation of an optically active
VI
Mo -oxodiperoxo complex 55 (Chart 13) and its application in enantioselective epoxidation
of trans-but-2-ene. Conversion to the trans-(1R,2R)-but-2-ene oxide was accomplished, in all
cases, with an yield of 70% and ee of up to 34%. Shortly afterwards, Kagan et al. [212]
reported another catalytic version of this reaction, showing its effectiveness over a range of
olefins which could be enantioselectively epoxidized in the presence of only 10 mol% of 55.
The highest ee obtained was only 35%, again for the epoxidation of trans-but-2-ene. The
reason advanced for such result was that an enantiofacial discrimination of the olefins and
kinetic resolution leading to enrichment of the enantiomers was not likely [212].
Chart 12
54
Chart 13
55
Mimoun then tested some chiral monodentate ligands noticing there was no observable
asymmetric induction [213]. In attempts to study the mechanism of oxygen transfer in this
epoxidation reaction by Modena and co-workers a series of reactions with chiral MoVI
catalysts as chiral tools was carried out to probe its mechanism. The highlight of this work
was use of complex 55 in the epoxidation of trans-oct-2-ene under the same conditions as
used by Schurig et al. affording the major enantiomer with 36% ee [214]. It was also
evidenced that certain chiral monodentate ligands, like, (−)-menthyl-phosphoric triamide and
N,N-dimethyl-(−)-menthylamine-N-oxide, can be used to give enantioselective epoxidations
(albeit low, 7–9% ee) which contradicted previous findings of Mimoun [213]. Still,
unfortunately, such studies were unable to provide clear-cut evidence on the oxygen transfer
mechanism from the MoVI-peroxo complex. Besides reactions using complex 55, Schurig et
al. [215] also prepared a set of other chiral MoVI-oxodiperoxo complexes based on a series of
enantiomerically pure hydroxyamides, (S)-piperidine lactamide (pla) (56), (S)-N,N-dimethyl-
3-phenyllactamide (dmpla) (57), (S)-2-hydroxy-3-methylbutanoic acid piperidineamide
(hmbpa) (58), (2S,3S)-2-hydroxy-3-methylpentanoic acid piperidineamide (hmppa) (59), (S)-
3-hydroxybutanoic acid piperidineamide (hbpa) (60), (S)-N-acetylprolinol (AcPro) (61) and
(S)-N-benzoylprolinol (BzPro) (62), schematized in Chart 14. A series of stoichiometric
epoxidations of prochiral, chiral racemic and chiral non-racemic olefins were used in a study
using the above mentioned complexes. The best results were obtained using trans-but-2-ene
with the complex derived from (S)-piperidinelactamide, MoO(O2)2·pla, (49% ee) and (S)-3-
methylpent-1-ene with either MoO(O2)2·pla (51% ee for the 2S,3S diastereomer and 49% for
the 2R,3S diastereomer) or with MoO(O2)2·dmla (55) (51% for the 2S,3S diastereomer and
49% for the 2R,3S diastereomer). Another relevant factor discovered was that
enantioselectivity was inversely dependent on the degree of alkyl substitution present in the
olefin, as reaction ee decreased in the following order: prop-1-ene > but-1-ene > 3-methylbut-
1-ene. Preferential formation of (R)-alkyloxiranes has been detected. The chiral
hydroxyamide ligands mentioned above with a variety of structural differences were screened
with an objective at gaining some insight into the influence of: (a) the size of the amide
component, (b) the degree of branching of the alkyl substituents, (c) presence of an additional
stereogenic centre, and (d) the type of chelate ring formed by the ligand with the metal, on the
enantioselectivity of the reaction.
Chart 14
56 57 58 59
pla dmpla hmbpa hmppa
61 62
60
hbpa AcPro BzPro
Since then it has been established that when the steric bulk in the main chain of the ligand
was increased depending on the type of amide ligand there was an increase or decrease in the
ee. The chelate ring geometry formed between the ligand and the metal was also shown to
affect enantioselectivity of oxirane formation, as this property increased in the following
order: seven-membered chelate > six-membered chelate > five-membered chelate. It was also
established that the addition of optically pure 1,2-alkanediol additives enhanced ees of the
oxirane products. For instance, epoxidation of trans-but-2-ene with MoO(O2)2·pla and one
equivalent of (2S,3S)-butanediol yields the corresponding epoxide with 93% ee. It was
suggested that a subsequent kinetic resolution of the oxirane products by a till then unknown
Mo-diol catalyst would lead to this enantiomeric enrichment.
It was only in 1999, a decade later, that Stirling and co-workers reported their work on
the use of chiral phosphinoylalcohol complexes of MoVI for the epoxidation of a number of
olefins [216]. The complexes were obtained from the reaction of chiral phosphinoyl alcohols
with MoO(O2)2 being suggested that coordination to the Mo center would occur through the
P=O group, according to Chart 15.
Chart 15
63 64 65 66
67 68 69 70
The resulting complexes were screened in the epoxidation of both terminal and di-
substituted olefins under both stoichiometric and catalytic conditions. The ee’s determined
were in the 2–39% range (see Table 7, for some selected results). In the case of complex
MoO(O2)2·70 epoxidation of hept-1-ene was carried out under both stoichiometric and
catalytic conditions, using tbhp as terminal oxidant (Table 7, entries 7 and 8). In the former, it
was raised that the mechanism most likely involves a direct attack of the olefin on one of the
peroxo oxygen atoms [217].
Table 7. Epoxidation of hept-1-ene with MoO(O2)2L (L = P ligands in Chart 15)

complexes and tbhp, under stoichiometric and catalytic conditions [216].
Ligand Conversiona / % ee / %
64 72 <2
65 55 0
66 77 <2
67 39 9
68 47 23
69 80 8
70 35 3
70 >70b 3
a
All reactions carried out under stoichiometric conditions (olefin : catalyst ratio of 10);
b
Carried out under catalytic conditions (olefin : catalyst ratio of 200).
Although ee’s were very low, ca. 3% in both cases, the catalytic reaction outperformed
most probably based on a different mechanism. Such mechanistic proposal had been
previously suggested by Thiel [218,219]. The authors ruled out a mechanism of coordination
of olefin to the metal center and opted for a situation in which two or more mechanisms were
at work for which predominance of a single one being determined by the actual reaction
conditions used. Based on a model (Chart 15, 63) it was also suggested that both O1 and O3
should be the transferred oxygen atoms as they are proximal to the chiral ligand, and asserted
that despite the environment near O1 being different to that around O2 it is the rate of oxygen
transfer that dictates the degree of enantioselectivity.
Chart 16
71 72
Shortly after, Yoon and co-workers reported the preparation of MoVI-oxodiperoxo

complexes based on (R)-piperidinylphenylacetamide 71 and (R)-piperidinylmandelamide 72
(Chart 16), and the first report of a catalytic epoxidation using this type of complex when
both trans- and cis-β-methylstyrene were transformed to the corresponding epoxides [221].
Under the conditions used, and despite moderate yields, they were able to achieve moderate
to good ees (26–81%). The highest ee (81%) was obtained using trans-β-methylstyrene and
complex 72.
Later on in 2004, the preparation of the first chiral MoVI-oxodiperoxo complexes 73, 74
containing N/O ligands (Chart 17) were reported [143].
Chart 17
73 74 75
Table 8. Aromatic olefin epoxidation using 2-(1-pyrazole)pyridineoxodiperoxo MoVI

chiral complex 75 and tbhp [222].
Olefin Conversion / % ee / %
31 2
86 1
28 0
37 5
44 6
49 n.d.
n.d. = not determined, due to small yield of epoxide.
Both have been tested in the catalytic epoxidation (2.5 mol% catalyst) of cyclooctene and
(R)-limonene in the presence of tbhp. Epoxidation of the latter was found to be unselective
and additionally ees were not reported. At the same time, a new report on the synthesis of 2-
(1-pyrazole)pyridineoxodiperoxo MoVI chiral complex 75 (Chart 17) has been presented,
which was used in a series of stoichiometric and catalytic olefin epoxidations with tbhp [222].
In the latter case the catalytic epoxidation reactions, led to almost no ee (Table 8). In further
attempts, excess styrene was treated with the same complex being benzaldehyde the sole
product. This arises from epoxide decomposition due to oxidative cleavage under the reaction
conditions used.
Under the same conditions an excess of cyclohexene originated the corresponding
epoxide along with cyclohexane-1,2-diol. This result led to the suggestion that catalytic olefin
epoxidations could be based on two possible mechanisms at work: (i) that suggested by Thiel
[218,219] involving oxygen transfer from the coordinated alkylperoxide addition and (ii)
direct transfer of an oxygen to the olefin from one of the peroxo oxygen atoms of complex 75
[217].
In a sequel of the work [221], it was proposed that the mechanism would involve a
coordinated alkylperoxide to the MoVI species, being this the active catalytic species [89].
Continuation of this subject [223], led to the study of series of chiral pyridines and pyrazoles,
Chart 18, to form chiral alkyl hydroperoxide MoVI species in situ. As in previous reports, no
enantioselectivity was observed in these reactions.
Chart 18
76 77 78 79
In face of these and previous results, lack of enantioselectivity was put down to the
following reasons: (1) presence of other chiral or achiral MoVI peroxy or peroxo species in
solution competing with the principal oxoperoxy complex (multiple catalytically active
species, which had been alluded to by Mitchell and Finney [224]); (2) labile nature of the
peroxy ligand, particularly at high temperature during reaction, leading to generation of a
number of competing diastereomeric transition states; (3) fast on/off exchange of ligands or
part of ligands from the coordination sphere of MoVI peroxy complex. In fact, weak
coordination has been recently proposed by Barlan and co-workers [225] to explain the lack
of success using such epoxidizing system. This as well as exchange between coordinated
alkyl hydroperoxides and alkoxides has recently been demonstrated on the basis of some DFT
calculations [89].
Fast on/off exchange of ligands or part of ligands mentioned above from the coordination
sphere of MoVI peroxy complex could have been the reason for lack of enantioselectivity in
the last system discussed above [223]. This is most probably the key reason why only poor to
fair enantioselectivities are obtained using oxoperoxo MoVI catalysts in olefin epoxidation.
Table 9. Catalytic oxidation of olefins, alcohols, amines and sulfides using

[MoO(O2)2(hpeoh)]− [hpeoh = o-C6H4(OH)−C(CH3)=N−OH] (80), H2O2
and NaHCO3 in acetonitrile [230,231].
Substrate Product Temp. / K Yield
298 91
96
98
90
70
90
87
97
313 91
97
353 81
98
63
89
60
88
96
96
96
78
Over the last decade the Thiel group have conducted exhaustive studies on this catalytic
reaction using 2-(pyrazol-3-yl)pyridinyloxodiperoxo MoVI complexes in both homogenous
[218,219] and in heterogeneous phases later on [226–228]. One combined study by this group
[229] using both NMR experiments and DFT calculations, evidenced that ligand dissociation
appeared to occur. Activation energies required (89–110 kJ·mol–1 in Thiel’s study) for ligand
dissociation are provided by high temperatures required for successful epoxidation reactions.
Such findings by Thiel and co-workers identified the principle reason why the
asymmetric induction is so weak in such systems. Another important reason in the case of the
oxodiperoxo MoVI complexes, is that the two electrophilic oxygen atoms are disposable to the
incoming nucleophilic olefin. In addition, and due to the symmetric disposition of the two
peroxo groups both enantiomers of the oxirane product should be obtained. Noticeably,
oxygen to olefin transfer rates are different, depending on the system, but not enough to
provide high enantioselectivities. Most probably, ligand dissociation from metal is the reason
why rates of oxygen transfer are not significantly different. This point had previously been
mentioned by Ross [216].
To circumvent this problem and develop catalysts that can reach high eneantioselective
products one must realize that: (1) stronger non-dissociating chiral ligands are to be used; (2)
the rate difference of the oxygen transfer from the two peroxo ligands must be accentuated;
(3) additional efforts must be spent developing and testing chiral monoperoxo complexes
holding strongly coordinating chiral ligands.
More recently some more works have been published concerning oxidation of a variety
of substrates using MoO(O2)2 complexes with pyridine and phenol oxime derivatives as
ligands [230,231] and using H2O2 as oxidant and in the presence or absence of NaHCO3 as a
co-catalyst. Results are summarized in Table 9, showing that conversions are quite high
across substrates.
Despite no ee’s have been reported it should be mentioned that in most cases selectivity
is quite high. In addition and according to the authors, use of NaHCO3 seems to lead to
different regioselectivity as evidenced by the oxidation of cinammyl alcohol which in its
presence yields the epoxide as the sole product with 70% (Table 9, entry 5). When in the
absence of NaHCO3 the same substrate under similar reaction conditions leads to
cinnamylaldehyde in 89% yield (Table 9, entry 14), at a different temperature though. In both
cases selectivity is 100% to the respective oxidation product.
At the same time the Gallindo group [232], reported the epoxidation of cyclooctene in the
presence of MoO(O2)2(4-MepyO)2 and using urea hydrogen peroxide complex (uhp) as
oxygen source. An additional novelty was the use of a room temperature ionic liquid (RTIL)
as reaction medium, particularly [C4mim][PF6] (1-butyl-3-methyl-1H-imidazol-3-ium
hexafluorophosphate). Substrate conversion was found to reach a maximum of 89%, giving
the corresponding epoxide with 83% yield.
Still, these works although recent, stress the demand for more robust catalysts based on
the point raised above in this chapter.
OXIDATIONS WITH [MOII(CO)2,3]2+ COMPLEXES AS PRE-CATALYSTS

Since the starting of the XXIst century, an increasing awareness on the use of pre-
catalysts has been observed [33,38,233]. Such pre-catalysts are simply organometallic MoII
carbonyl complexes which can be oxidized to the dioxo MoVI homologues. The very first
example of a complex of this family was CpMoO2Cl reported in 1963 by Cousins and Green
[234], obtained by oxidation of [CpMo(CO)3]2 and CpMo(CO)2(π-C3H5). The dioxo complex
mentioned above was synthesized in very low yields and surprisingly as the only isolable
product from air oxidation of CpMo(CO)2(π-C3H5) in the presence of HCl.
From the recent evolution on the use of the latter carbonyl complexes it was found that
these undergo oxidative decarbonylation to yield the corresponding organometallic MoVI
dioxo congeners [235]. In that work the group of Gonçalves showed possible the direct use of
the CpMo(CO)3Cl carbonyl complex as a precatalyst for olefin oxidation using tbhp. It was
also found that under the catalytic reaction conditions the tricarbonyl complex rapidly yields
CpMoO2Cl which was reported to be the active species. Comparison of the catalytic
performance with the use of the dioxo complex was found to produce similar results, both
complexes reaching identical performance in cyclooctene epoxidation (complete substrate
conversion with 100% selectivity to the epoxide after 6h).
After those results have been reported, other works concerning the direct use of MoII
carbonyl complexes as precatalysts, which are then oxidized in situ to yield the active species,
followed. The set of catalytic systems tested since then is resumed in Table 10, accounting
not only for the catalytic system used (precatalyst complex, oxidant and olefin) but also to its
achievements.
From data shown in Table 10 concerning cyclooctene epoxidation it should be mentioned
that the work of Abrantes et al. [236] has used microwave radiation as a convenient method to
perform the heating of the catalytic tests, as compared with conventional oil bath heating.
Such approach has proved quite adequate as kinetics as well as conversion and yields are
superior (Table 10, entries 2, 3 and 4, 5) for both the case of cyclooctene and limonene.
In the case of primary alcohol oxidation yielding the corresponding aldehydes, excellent
selectivities have also been reached. The results show that the Mo acetylide complex is very
efficient catalyst for accomplishing such transformation [238], with maximum selectivity.
Such system can very well tolerate electron-rich as well as electron-withdrawing substituents
on aromatic ring. According to the authors, the water soluble nature of the catalytically active
species, an oxo-peroxo Mo acetylide moiety and formation of organic phase of the product
(aldehyde) have enabled very easy and efficient recycle of this homogeneous catalyst even up
to five recycles without appreciable loss in conversion and aldehyde selectivity.
More recently, and derived from the above mentioned Cp complexes, a series of
complexes containing the Cp ligand with ansa bridges were also prepared and its catalytic
performance reported. The original idea behind the synthesis of ansa-bridged compounds was
to hinder Cp-loss after possible intermediate ring slippage. Ansa-bridged derivatives have
been used to introduce chirality in the system by transforming the bridging C atoms into
chiral centers. However, it turned out that ansa-bridges with only two carbon atoms in the
bridge are not sufficiently stable, due to considerable ring strains under oxidative conditions
[239]. Introducing chirality with a chiral substituent on the Cp-ring has also been attempted.
Table 10. Catalytic performance in olefin or primary alcohol oxidation using

Cp’Mo(CO)3X (X = Cl, CH3, Aryl ; Cp’ = Cp or Cp derivatives) complexes.
Complex
Oxidant Substrate Conversion Selectivity Ref.
Cp’ ; X
Cp ; Cl 81 tbhp 100 100 235
Cp ; CH3 82 tbhp 94 (mw) 100 236
86 100
tbhp 91 (mw) 100
80 100
Cp–COProBz ; CH3 83 tbhp 100 84 237
Cp-CCPh ; C≡C–Ph 84 H2O2 86 92 238
87 87
90 90
60 88
65 91
72 82
70 75
82 88
82 85
In the case of the use of N-heterocyclic carbene Cp derivative ligands, reported by

Royo’s group [240] these were not as active (Table 11, last 3 entries) as the regular ansa-Cp
derivatives reported by Kühn. In fact only one of the catalysts, holding the most bulkier Cp
derivative showed a high activity towards cyclooctene epoxidation (Tabel 11, last entry).
Table 11. Catalytic activity of ansa-CpMo(CO)2X (X = CO, I) in cyclooctene
epoxidation.
Complex Yield Ref.
100 239
85
100
86
100
87
100
88
100
89
25
90
25 240
91
11
92
91
93
Table 12. Catalytic activity of Mo(η3-C3H5)X(CO)2L complexes in olefin epoxidation.
X L Conversion / % Ref.
Cl CH3CN 94 100 241
N N 95 241
95
88 241
96
100 241
97
99 242
98
100 243
99
Br CH3CN 100 100 241
100 241
101
99 242
102
64 244
103
45 244
104
80 245
105
33 245
106
64 246
107
In a different though parallel perspective, related catalytic systems using Mo(η3-
C3H5)X(CO)2Ln (X = Cl, Br; Ln = mono or bidentate lewis base ligands) complexes have also
been reported in recent years [241-246]. These works screened over quite some ligands, as
evidenced in Table 12.
Table 13. Catalytic activity of MoX2(CO)3L complexes in cyclooctene epoxidation.
X L Conversion / % Ref.
Br CH3CN 108 100 247
88 247
109
I CH3CN 110 81 247
63 247
111
13 248
112
9 248
113
In fact it was found that catalytic activities were very dependent on the type of ligand
used. Generally the ligands used relied on N,N’ bidentate ligands but in some cases it was
found that when the ligands hold N–H moieties deactivation does occur with conversions
dropping down drastically (Table 12). More recently the use of carbene ligands in these allyl
complexes has been reported showing good activities using H2O2 as oxygen source [243].
Epoxide yields were found to reach almost 100 % in many cases stressing the usefulness of
such association. In fact such system (Tabel 12, entry 6) was found to be more active in
cyclooctene epoxidation than the Cp counterparts (Table 11, 3 last entries).
The use of related though different complexes from the MoX2(CO)3Ln (X = Br, I; Ln =
mono or bidentate Lewis base ligands) heptacoordinate halocarbonyl family were also
reported to possess catalytic activity in olefin epoxidation [247,248]. These complexes were
developed in pioneering work by Baker for catalytic applications other than oxidation [249].
However, such systems were found to have quite high performances, Table 13, although it
was found very recently that such systems suffer from the same ligand dependency which
leads in some cases to deactivation. This is true when ligands hold NH moieties as already
discussed a few lines above in this chapter [248].
In fact a survey on such ligands has permitted to establish an important ligand structure-
catalytic activity relationship stressing the importance of the inexistence of deactivating N–H
moieties. This is shown in Figure 1.
Attempts at understanding the mechanistic aspects of the transformation of the MoII
carbonyl precursors into their MoVI dioxo congeners by means of an oxidative
decarbonylation process have been the aim of quite some works. To this concern the
chemistry of CpMoO2X and CpMo(CO)3X (X = Cl, Br, CH3) complexes has by far been the
mostly studied across years as compared to the other mentioned carbonyl systems based on
the Mo(η3-C3H5)X(CO)2Ln or the MoX2(CO)3Ln (X = Cl, Br, I; Ln = mono or bidentate Lewis
base ligands) halocarbonyl families reported above in this chapter.
The first records dealt mainly with the development of proper methods of preparing the
CpMoO2Cl complex from CpMo(CO)3Cl. Cousins and Green were the first authors to
rationalize several synthetic methods for obtaining the CpMoO2X (X = Cl, Br) complexes
(Chart 19) [250-252]. One of the methods consists in the irradiation of [CpMo(CO)3]2 in a
solution of the haloform of interest (either chloro- or bromoform) and with O2, which affords
the desired CpMoO2X (X = Cl, Br) complexes.
Chart 19
81, 114
Both derivatives showed to be stable under inert N2 atmosphere, decomposing slowly

under air and rapidly in solution. As in the first method, yields were also reported to be very
low. This is the result of relatively unspecific synthetic pathways, leading also to other
species such as mono oxo and dimeric complexes. These difficulties have surely been the
cause for a gap between these early works and the next publications dealing with Cp dioxo
molybdenum complexes which have emerged in the late 1980’s [253,254]. The synthesis of
Cp*MoO2Cl [Cp* = η5-C5(CH3)5] was obtained by oxidation of the dimeric carbonyl
complex [Cp*Mo(CO)2]2 with O2 in chloroform and subsequent treatment of this
intermediary with PCl5, yielding a μ-oxo bridged dimer, Scheme 5. This complex exhibited
good thermal stability being also able to be manipulated in dry air, along with both ease of
preparation and separation from other reaction products. Such synthetic procedure was a
substantial improvement in comparison to its Cp counterpart previously described by Green

[234].
Several other methods have emerged in the following years for the synthesis of
Cp’MoO2Cl (Cp’ = Cp, Cp*) and will be briefly addressed in the following lines. The several
synthetic pathways developed for Cp*MoO2Cl (58) are also summarized in Scheme 5.
This scheme stresses the different synthetic routes as well as its efficiencies in both terms
of reaction time and product yield. In particular irradiation of Cp*Mo(CO)3Cl in toluene
under an O2 purge and UV radiation for 2 h ,yields Cp*MoO2Cl [255]. In a parallel pathway
the chloride carbonyl Cp*MoCl4 precursor complex discarded the need to conduct the
reaction in chlorinated solvents.
Figure 1. Ligand structure–catalytic activity relationship from MoII based complexes for cyclooctene
conversion. The numbers adjacent to ligand names refer to the respective reference.
Scheme 5. Synthetic pathways for preparation of Cp*MoO2Cl (see text for details).
This complex was found to yield Cp*MoO2Cl by reaction with aqueous NaOH in the
presence or absence of air [256]. Reaction times lower than 30 min, in the absence of air (N2)
led to the formation of Cp*MoOCl2. On the other hand in the presence of air Cp*MoO2Cl is
obtained. In this context the former complex seems as the logical intermediate to the dioxo
complex. When reaction times longer than 30 min are used the formation of the μ-bridged
oxo dimer [Cp*MoO2]2O is obtained. Such dimeric complex is likely formed via hydrolysis
of Cp*MoO2Cl generating Cp*MoO2OH, which then undergoes condensation by loss of H2O.
Despite this, the base used in these reactions is not innocent on the products obtained. In fact,
when Cp*MoCl4 reacts with t-BuNH2 in the presence of water and air the [Cp*MoO3]–
anionic trioxo complex is formed being isolated as its [t-BuNH3]+ salt. Subsequent treatment
of this complex with gaseous HCl gives Cp*MoO2Cl neatly. A few other methods have since
then been reported [257,258], including treatment of [Cp*Mo(CO)2]2 with 30% hydrogen
peroxide and HCl [258].
A major improvement on the synthesis of (η5-C5R5)MoO2Cl (R = H, CH3, CH2Ph (Bn))
complexes from their corresponding and readily available (η5-C5R5)Mo(CO)3Cl precursors
was reported in 2003 [259]. The desired complexes could be obtained in yields reaching 75%
by stirring a CH2Cl2 solution of the carbonyl precursors with excess of tbhp for ca. 2 h
(Scheme 5). Dimethyldioxirane was found to be unable to oxidatively decarbonylate to (η5-
C5R5)MoO2Cl in contrast to other systems [260]. Comparison with previously described
synthetic routes, evidences the latter method of oxidative decarbonylation of (η5-
C5R5)Mo(CO)3Cl provides a more general route comprising different derivatives of the Cp
ring. All three compounds originally described in that work can be handled in air for brief
periods of time, but are rather moisture sensitive in solution. (η5-C5Bn5)MoO2Cl is
significantly more stable than its Cp and Cp* congeners, probably due to steric bulk effect of
the Cp ligand. Similarly, a striking increase in stability, even in comparison to Cp*MoO2Cl
had also been previously observed with the compound (η5-C5Ph4R)MoO2Br (R = 2,5-
dimethoxyphenyl) [261].
At the same time Poli et al. reported speciation studies of Mo complexes containing the
Cp* ligand over the entire pH range in an essentially pure aqueous environment by several
methods, including stopped-flow kinetic analysis, on-line electrochemical flow-cell and
electrospray mass spectroscopy [262–264]. Such studies revealed the existence and stability
of Cp*MoO2OH and [Cp*MoO2]+ complexes as a function of pH. The authors also concluded
that the inertness of the Cp*–Mo bond, resists hydrolysis down to pH zero. As a consequence
this blocks three coordination positions, rendering the Cp*–MoVI species unable to form
extended oligonuclear aggregates.
Although many efforts have been devoted to the preparation of the above mentioned (η5-
C5R5)MoO2X [R = H, CH3, CH2Ph (Bn); X = Cl, Br, CH3] many other studies dealt with the
catalytic applications of these and other complexes not only in olefin epoxidation (the
majority of examples) but also in the oxidation of other substrates.
The catalytic activity of dioxomolybdenum complexes containing cyclopentadienyl
ligands was – until recently – solely examined for Cp*MoO2Cl by Bergman and Trost [255].
This complex was shown to act as active catalyst for the epoxidation of several olefins (such
as cyclooctene, geraniol, 1,2,4,5-tetramethylcyclohexa-1,4-diene), as long as they do not
include any electron-withdrawing groups. Apart from tbhp, other alkyl hydroperoxides such
as cumyl hydroperoxide and n-hexylhydroperoxide could be used as oxidants. However,
when H2O2 and thp were used no catalytic reaction occurred and the oxo-peroxo complex
Cp*Mo(O2)OCl was formed. When in the absence of olefins, the authors found that tbhp
would react with Cp*MoO2Cl yielding also the Cp*Mo(O2)OCl complex. Catalytic reactions
performed with the isolated Cp*Mo(O2)OCl did not lead to any oxidation products.
Consequently this species was considered to be an unwanted side product, and being
concluded that the active species cannot be a η2-coordinated peroxo complex.
These results were later supported by Roesky et al. who analyzed the X-ray crystal
structure of Cp*Mo(O2)OCl and also described this compound as being not active as olefin
epoxidation catalyst in the presence of excess tbhp, thus confirming previous findings [265].
Apart from formation of Cp*Mo(O2)OCl, the catalyst precursor Cp*MoO2Cl seems to
maintain its integrity during the catalytic reaction, showing no observable oxidation of the
Cp* ligand as evidenced by 1H NMR data [255]. The effect of the alkyl peroxide used on the
relative rate of the epoxidation reaction was investigated and the obtained rates were
consistent with formation of an intermediate species in which the alkyl group of the peroxide
moiety is intact. In this way, relative rates depend on structure of the alkyl group of peroxide
and catalyst loads of 2–5% were used depending on substrate and reaction temperatures
spanned from r.t. (room temperature) to 333 K.
The study of the catalytic properties of the (η5-C5R5)MoO2Cl [R = H, CH3 (Me), CH2Ph
(Bn)] complexes as catalysts for the epoxidation of cyclooctene, styrene and 1-octene has
been extended [259]. Reactions were conducted at 328 K using catalyst loadings of 1 mol%,
with tbhp as oxidant. Influence of ring substituents on catalyst activity was studied in detail
for cyclooctene. Both (η5-C5H5)MoO2Cl and (η5-C5Bn5)MoO2Cl complexes show good

activity, reaching 100% conversion after 4 h reaction time. However, in a second and third
catalytic run (by addition of new substrate) the complex (η5-C5Bn5)MoO2Cl maintains most
of its activity, while that of the Cp derivative declines strongly due to catalyst decomposition.
Similarly (η5-C5Me5)MoO2Cl reaches only about 60% of the activity of the other derivatives
in the first run and shares the same decomposition problems observed for (η5-C5H5)MoO2Cl
under catalytic conditions. Due to its high stability and activity, catalytic runs were performed
using a catalyst load of (η5-C5Bn5)MoO2Cl as low as 0.1% under the same reaction
conditions. TOFs (turnover frequencies) of 4000 h-1 were achieved, and lowering the Mo
compound load to 0.01%, values of 20000 h-1 were reached. However, at these low catalyst
loadings the residual amount of water present in the system gains increasing influence on the
catalytic performance after some time and consequently, the catalytic activities decrease
considerably after 1 h reaction time for the lowest catalyst amounts applied [259]. According
to the authors, the high activity of this complex, despite its higher steric bulk, was ascribed
both to its higher stability towards moisture and the lower electronic density at the Mo center,
in comparison to the derivatives (η5-C5Me5)MoO2Cl and (η5-C5H5)MoO2Cl, due to a weaker
Mo-ring bond, as reflected in 95Mo NMR and vibrational spectroscopy. Epoxidation of
styrene and 1-octene was also successful using (η5-C5R5)MoO2Cl [R = H, CH3, CH2Ph (Bn)],
the best results being again obtained with complex containing the bulkier ligand. Ring
opening of the styrene epoxide to the diol is not significant under the conditions applied; 1-
octene, being an unactivated, unfunctionalized olefin reacts significantly slower than the other
substrates.
When Gonçalves first reported on the use of CpMo(CO)3Cl as a precatalyst that could be
used directly for catalysis which would undergo oxidative decarbonylation in situ it was
mentioned that CpMoO2Cl was the active catalyst [235]. Such statements were published
based on several spectroscopic observations in which the authors proved that the oxidative
decarbonylation process proceeds via the release of CO rather than CO2. This means that in
the process CO ligands are not involved in any oxidation process.
It should also be mentioned, however, that in a recent work an in-depth study based on
kinetic data has been accomplished by the Colbran group [266]. According to the authors and,
given the marked dependence of catalytic efficiency on the cyclopentadienyl substituent, no
(η5-C5Ar5)MoO2Cl (Ar = aryl group) complex had been screened for epoxidation catalysis.
That study was motivated by the fact that the same authors had in a previous report
demonstrated that (η5-C5Ar5)MoO2X complexes may exhibit exceptional stability, such as the
[(η5-C5Ph4R)MoO2Br] (R = 2,5-dimethoxyphenyl) complex already mentioned previously in
this chapter [261]. Using this latter mentioned complex it was found that the epoxidation
mechanism must involve, most probably, three species, according to Scheme 6.
According to the model, the initial [(η5-C5Ph4R)MoO2Br] (R = 2,5-dimethoxyphenyl)
complex leads to a species A which is catalytically active, though it transforms into a
transient species B. This latter species is predicted to be inactive, though it converts into
species C which will be the active species. By the end of the catalysis run, species C will be
the only Mo-containing species present. Based on 1H NMR data, species C is formed by loss
of the cyclopentadienyl moiety. According to the kinetic model, Scheme 6, species C is the
active catalyst that dominates the faster phase. Recharging the catalytic system with
cyclooctene and tbhp at this point leads to immediate catalysis consistent with species C
remaining present and active at the end of the run.
Scheme 6. Mechanistic model proposed according to kinetic data (k1 ≈ k2 > 5 × 10–5 s–1 ; 35·kA ≈ kC =
7.3 (±0.3) × 10–5 s–1 ; kB ≈ 0 s–1) [266].
Two insights followed from this information. First, (perarylcyclopentadienyl) MoVI dioxo
species do catalyze alkene epoxidation. Second, the Cp ligand is lost from Mo as the catalysis
proceeds, leading to the in situ generation of a much more efficient catalyst. The latter finding
evidenced that loss of the Cp’ ligand from a Cp’MoO2X catalyst, even if only slight, should
always be considered in alkene epoxidation catalyzes, because the thus-formed Mo species C
may be the most active catalyst. Although, Poli’s group has revealed a varied and rich
aqueous chemistry in its speciation work under varying pH conditions as already mentioned
in this chapter [264], indeed they have also showed that loss of the Cp* ligand may occur
under certain conditions [267]. In this way presumption of complete stability for an
alkylcyclopentadienyl MoVI oxo catalyst during epoxidation catalysis may be unfounded.
Difficulties that have been previously encountered in reconciling kinetic data
[33,94,95,101,259,268,269] with trends in parameters such as the steric bulk of the ring
substituents as well as either the tendency or ability of the Cp to undergo catalysis-facilitating
ring slippage was found to have its cause in loss of the alkylcyclopentadienyl ligand, even in
trace amount, to afford a more active MoVI (per)oxo species.
Most recently the mechanism of olefin epoxidation using CpMo(CO)3(CH3) has been
clarified based on both kinetic data and DFT calculations [270,271]. According to the authors
this complex has quite some differences as compared to its homologue CpMo(CO)3Cl. It was
found for the former that the mechanism proceeds through a combined cycle involving two
possible pathways, Scheme 7.
Those works have finally shed some light on what was happens behind the scenes
concerning such catalysts with Cp ligands. Of course it is now hoped that work is to be
carried out to reveal how other related systems behave, either Mo(η3-C3H5)X(CO)2Ln or
MoX2(CO)3Ln (X = Cl, Br, I; Ln = mono or bidentate Lewis base ligands) halocarbonyl
families which are also active players in such chemistry.
Scheme 7. Overall mechanism for the oxidation of CpMo(CO)3(CH3) by tbhp and the epoxidation
activities of the resulting oxidated complexes CpMoO2(CH3) and CpMoO(O2)(CH3) [270,271].
CONCLUSION
The present chapter aimed at an overview of recent literature concerning the role of Mo
complexes in oxidation chemistry. Behind such interest one can find the usefulness of the
industrial processes developed by ARCO and Halcon in the late 1960’s [81,82]. The first
complexes were developed about 50 years ago, although catalytic applications have only been
exploited with more interest starting in the 80’s decade of the XXth century, promoted by the
mentioned industrial processes that raised the interest of the scientific community.
Even though this represents a time span of 30 years to the present days it was only in the
last 10-15 years or so that this chemistry has been properly explored. In fact many works
devoted not only to develop catalytic applications, mainly in olefin epoxidation, but also to
understand what happens behind the scenes during the catalytic cycle. Proof of this are many
works which have reported on kinetics and DFT studies of the respective mechanisms, as
discussed in this chapter.
Although literature review was accomplished exhaustively, it certainly was not complete.
Despite this, the view presented here shows the panorama of the present state of the art
concerning Mo oxidation chemistry as given by three main topics discussed above, namely
[MoVIO2]2+, [MoVIO(O2)]2+ and [MoII(CO)2,3]2+ (pre-)catalysts. After reading this chapter one
may think that in a way all topics merge to a common end, MoVI-oxo core, and in fact they
do. This is evidenced since the dioxo core may lead to oxo-peroxo and that the carbonyl
precursors originate the dioxo and subsequently the oxo-peroxo (Scheme 7). Regardless of
this, the fact is that imagination seems to be the limit as given by the increasing number of
works dealing with several aspects. This ranges from preparing different (and more efficient)
catalysts, testing new oxidants and reaction conditions or by performing oxidation reactions
in substrates other than olefins. This latter aspect was clearly illustrated by some fine
examples of sulfide oxidation, whose reactions in some cases were shown to be tuned so that
asymmetric products could be obtained. Still, there is much work to do especially in the field
of the organometallic derivatives whose chemistry is still in its early days.
It is therefore aim of this chapter to provide the reader with a critical update on the most
relevant literature that may help pointing the way ahead from this point onwards.
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Chapter 3
HOMOGENEOUS CATALYSTS BASED

ON BIS(IMINO)PYRIDINE COMPLEXES OF IRON,
COBALT, VANADIUM AND CHROMIUM: THE KINETIC
PECULIARITIES OF ETHYLENE POLYMERIZATION
N.V. Semikolenova*, A.A. Barabanov, L.G. Echevskaya,

M.A. Matsko and V.A. Zakharov
G.K. Boreskov Institute of Catalysis,
Siberian Branch of the Russian Academy of Sciences
630090, Novosibirsk, Russian Federation
ABSTRACT
The family of highly active ethylene polymerization catalysts based on the
complexes of transition metals with bis(imino)pyridine ligands has been intensively
studied in the last ten years. In this study we summarize the known data and present new
kinetic results on the ethylene polymerization over homogeneous catalysts based on
Fe(II), Co(II), V(III) and Cr(III) bis(imino)pyridine complexes with close ligand
framework (2,6-(2,4,6-R3LMeCln, where R= H, Me, i-Pr, t-Bu, L=(C6H3N=CMe)2C5H3N,
M= Fe(II), Co(II), V(III), Cr(III), n=2,3).
The effects of the activator nature (different samples of methylalumoxane (MAO), or
aluminium trialkyls) and polymerization conditions on the activity of these complexes
and the resulted PE structure (molecular weight, molecular weight distribution, content of
methyl and vinyl groups) have been studied.
For the first time the number of active centers and propagation rate constant for
ethylene polymerization with Fe(II), Co(II), Cr(III) and V(III) bis(imino)pyridine
complexes, activated with MAO and Al(i-Bu)3, have been determined using method of
polymerization inhibition by radioactive carbon monoxide (14CO).
The experimental data obtained in comparable conditions have shown that the
catalytic properties of bis(imino)pyridine complexes ( polymerization activity, number of
* Corresponding author. Tel.:+7(383)326 95 51, E –mail address: N.V.Semikolenova <nvsemiko@catalysis.ru>

98 N.V. Semikolenova, A.A. Barabanov, L.G. Echevskaja et al.
active centers and propagation rate constant, copolymerization reactivity, composition of

optimal activator, formation of single site or multiple sites catalytic system, catalysts
thermal stability and PE structure) are mainly determined by transition metal center of
complex. The size of the substituents R in 2,6-positions of arene ring in the ligand L
affects the number of active centers and molecular weight of PE as well.
Keywords: 2,6-bis bis(imino)pyridine complexes of iron (II), cobalt (II), chromium (III) and
vanadium (III), ethylene polymerization, polyethylene, molecular weight distribution
1. INTRODUCTION
The olefin polymerization catalysts based on soluble well defined transition metal
complexes, providing access to polymers with new or improved characteristics, is currently a
subject of great academic and industrial interest. During the 80s large efforts were devoted to
creation of the group 4 metallocene systems. The advances in the development of metallocene
and their related half-sandwich (“constrained geometry”) catalysts [1] gained the insight into
the nature of the activated species and the possibilities for controlling the polymeric products
structure and resulted in a number of commercial processes for preparation of new
polyolefinic materials. To expand the range of the produced polymers, considerable efforts
have been devoted to the discovery of new families of catalysts based on the complexes of
non-metallocene nature. An important advance in this direction was made by Brookhart and
co-workers, who have shown that nickel and palladium complexes with bulky a-dimine
ligands are capable of polymerizing ethylene to high molecular weight polymers [2]. This
discovery has stimulated rapid development of new generation of “post-metallocene”
catalysts. Advances in this field are broadly covered in a number of reviews [3-6].
At present, complexes of transition metals with polydentate nitrogen-containing
ligands are considered as one of the most promising families of post-metallocene catalysts. It
was reported by Brookhart [7,8] and Gibson [9,10] that 2,6-bis(imino)pyridine complexes of
iron and cobalt (Scheme 1, RnLMCl2, where M=Fe(II) or Co(II), L= 2,6-bis(imino)pyridine
ligand, Rn - the substituents in the arene ring of the ligand L ) when activated with
methylaluminoxane (MAO) form extremely active homogeneous catalysts for ethylene
polymerization to linear polyethylene (PE). This type of catalysts is easer to synthesize and
they are more tolerant to polar groups than metallocenes. In the last ten years the catalysts
based on bis(imino)pyridine complexes have attracted much academic and industrial interest
and were intensively studied.
Scheme 1 The structure of iron and cobalt 2,6-bis(imino)pyridine complexes (M=Fe(II) or Co(II),
R= Me, R1,R2,R3 = H, Me, Et, t-Bu, i-Pr)
Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 99
During further investigations it was found [11-15] that iron bis(imino)pyridine complexes
can be activated with common aluminium trialkyls (AlMe3, AlEt3, Al(i-Bu)3, Al(n-Oct)3), that
substantially simplifies the catalytic systems and broadens the possibilities of their use in the
polymerization processes. Highly linear PE samples are obtained with iron and cobalt
bis(imino)pyridine complexes. The values of molecular weight (Mw) and molecular weight
distribution of the resulted PEs are governed by the substituents in phenyl rings of the ligand
[5,7-10], giving the possibility to obtain polymers with different value of Mw – from
oligomers to high molecular weight PE. Later, it have been shown that vanadium(III) [16-18]
and chromium(III) [19-21] complexes with bis(arylimino)pyridine ligands can be regarded as
promising catalysts for ethylene polymerization.
Commonly, in the literature the data on the catalytic properties of the systems based on
bis(imino)pyridine complexes of various composition are discussed separately. Such an
approach hinders the ascertainment of patterns in the catalytic properties of these systems
since the catalytic activity and the molecular structure of the resulting PE are affected by the
polymerization conditions (catalyst concentration, the nature and amount of the activator,
polymerization temperature etc.).
In this study we summarize the known data, including those obtained by ourselves [12,
22-35] and present new results on the polymerization properties of homogeneous catalysts
based on Fe(II), Co(II), V(III) and Cr(III) bis(imino)pyridine complexes. A detailed study on
the effect of the activator nature and the ligand composition on the catalytic behavior of
bis(imino)pyridine complexes and the resulting PE structure has been undertaken. The
experimental data have been obtained under comparable conditions allowing us to reveal the
effect of the transition metal on the catalytic properties of the homogeneous catalysts based
on bis(imino)pyridine complexes. For ethylene polymerization over Fe(II), Co(II), Cr(III) and
V(III) bis(imino)pyridine complexes, activated with MAO and Al(i-Bu)3 the number of active
centers and propagation rate constant have been determined using the method of
polymerization inhibition by radioactive carbon monoxide (14CO).
The experimental data obtained under comparable conditions have shown that the
catalytic properties of bis(imino)pyridine complexes ( polymerization activity, number of
active centers and propagation rate constant, copolymerization reactivity, composition of
optimal activator, formation of single-site or multiple-sites catalytic system, catalysts thermal
stability and PE structure) are mainly determined by transition metal center of complex. The
size of the substituents R in 2,6 positions of the arene ring in the ligand L affects the number
of active centers and molecular weight of PE as well.
2.1. CATALYSTS BASED ON RNLFECL2

Effect of Activator
The data on the activity of homogeneous catalytic systems composed of 2,6-Me2LFeCl2

with different activators and structure of the resulted PE are summarized in Table 1.
Table 1. Ethylene polymerization over 2,6-Me2LFeCl2 and different activators
3) 4)
Run Activator Yield Maximum Mw, Mw/ Content per Content per
Kg activity, × 10- Mn 1000 С PE molecule
3
PE/
Kg PE/ mol СН3 СН= СН3 СН=
mol Fe
Fe bar min СН2 СН2
bar
1)
1 MAO 9100 500 71 8.3 1 0.8 1.2 0.9
1)
2 MAO (50) 11000 330 75 4.6 0.8 1.0 1.0 1.2
2)
3 MMAO 6800 430 - - - - - -
1)
4 AlMe3 12300 300 106 12.0 1.9 0.7 1.5 0.5
2)
5 Al(i-Bu)3 7600 250 115 11.0 1.5 0.6 1.4 0.6
1)
6 Al(n-Oct)3 12300 320 46 6.3 1.4 1.2 1.1 0.9
1)
7 Ph3C[B(C6F5)4] 470 20 - - - - - -
+ Al(i-Bu)3
1)
Polymerization in toluene at 35 ºC, ethylene pressure 2 bar, for 30 min, [Fe] =1.4 × 10-5 mol/l,
Al/Fe=500.
2)
Polymerization in heptane, all other conditions as run 11)
3)
Calculated according to Figure 1
4)
IRS data
The kinetic curves for correspondent polymerization runs are shown on Figure 1.
600
1
Activity, kg PE/mol Fe bar min
500
400
2
4
6
300
200 5
100
0
10 20 30
Time, min
Figure 1. Kinetic curves for ethylene polymerization over the catalysts composed of 2,6-Me2LFeCl2 and
different activators: (1) MAO; (2) МАО(50); (4) AlMe3 ; (5) Al(i-Bu)3 (6) Al(n-Oct)3.(Number on the
curve corresponds to the number of the experiment in Table 1).
All examined systems exhibited low thermal stability and virtually lost polymerization
activity at temperatures above 50 ºC. At 35 ºC highly active catalytic systems providing high
PE yield were formed upon activation of 2,6-Me2LFeCl2 with two different MAO samples
(commercial MAO with AlMe3 content ~0.5 M and MAO sample with the reduced content of
AlMe3 ( ~ 0.001 M of AlMe3, MAO(50)); MAO modified with Al(i-Bu)3 (commercial
sample, MMAO) and aluminium trialkyls (AlMe3, Al(i-Bu)3 and Al(n-Oct)3 ) (Table 1). In
contrast to metallocene catalysts, a borate activator was not effective for iron
bis(imino)pyridine catalysits (Table 1, run 7). The examined catalysts exhibited high initial
activity decreasing in the course of polymerization (Figure 1). The system stability and PE
yield depend on the activator nature. The catalyst obtained upon activation of iron complex
with commercial MAO exhibited very high initial activity, but the latter rapidly fell with the
polymerization time (Figure 1, curve 1). The systems formed by 2,6-Me2LFeCl2 interaction
with aluminium trialkyls (AlMe3, Al(n-Oct)3), provided higher PE yield (Table 1, runs 4, 6)
than that obtained in presence of MAO and MMAO (Table 1, runs 1 and 3) due to the higher
stability of these systems (Figure 1, curves 4, 6). The catalysts formed by interaction of iron
complex with Al(i-Bu)3 and MMAO, soluble in aliphatics, show high initial activity in the
polymerization in heptane medium (Table 1, runs 3 and 5). These systems were less stable
than that prepared using MAO purified from AlMe3 (MAO(50)), AlMe3 and Al(n-Oct)3
(Figure 1), causing the reduced yield of PE.
The obtained polyethylene samples were highly linear (about one -CH3 and vinyl
terminal groups per one PE molecule) (Table 1). The values of molecular weight and
polydispersity (Mw/Mn values) depend on the activator nature. Data in Table 1 and Figure 2
show that in the presence of MAO (50), PE with the lowest polydispersity was obtained
(Mw/Mn=4.6, Table 1, run 2 , Figure 2, curve 2), whereas the Mw/Mn value of PE sample
prepared using commercial MAO was noticeably higher (Mw/Mn=8.3, Table 1, run 1, Figure
2, curve 1).
1,0 2
6
0,8
d Wf/d log M
1
0,6
5
0,4
0,2
0,0
2 3 4 5 6 7
Log M
Figure 2. MWD of PE produced with homogeneous catalysts composed of 2,6-Me2LFeCl2 and different
activators: (1) MAO; (2) МАО(50); (5) Al(i-Bu)3 (6) Al(n-Oct)3.(Number on the curve corresponds to
the number of the experiment in Table 1.) ( Wf= weight fraction, M=molecular weight.)
Polymers prepared with the systems (2,6-Me2LFeCl2/Al(i-Bu)3) and (2,6-

Me2LFeCl2/AlMe3) were characterized by the highest Mw values (Table 1, runs 4, 5),
whereas using Al(n-Oct)3 as activator the PE sample with the lowest molecular weight was
obtained (Table 1, run 6). Broad molecular weight distribution (MWD) of the polymers
formed in the presence of the catalysts composed of 2,6-Me2LFeCl2 and different activators
indicate that a set of different active sites is formed in these catalytic systems, so the catalysts
of this type should be regarded as multiple-site catalysts.
Effect of the Ligand Composition
Changes in the ligand environments of iron bis(imino)pyridine complexes results in

changes in catalysts productivity and polymer molecular weight [5,7-10]. As it was shown in
[10], in presence of MAO as activator, ketimine catalysts ( R= CH3-, Scheme1) are more
productive than their aldimine analoges (R = H-, Scheme1). Modification of the aryl ring
attached to the imino nitrogen atoms has the pronounced effect on the catalysts activity and
the molecular weight of the produced PE [5, 7-10]. The data on the catalytic behavior of iron
bis(imino)pyridine complexes Rn-LFeCl2 bearing different substituents in 2,6 –position in the
aryl ring of the ligand are collected in Table 2 and Fig. 3.
Table 2. Effect of the substituents R on the activity of Rn-LFeCl2/MAO catalysts and

molecular weight characteristics of the PE produced.
3)
Run Rn Yield Maximum activity, Mw, Mw/Mn
Kg PE/ mol Fe bar × 10-3
Kg PE/ mol Fe bar min
1* 2-Me 12650 770 - -
2 2,6-Me2 9100 500 71 8.3
3 2,6-i-Pr2 6650 980 220 20.0
4 2,6-Cl2 5800 1100 15 2.9
-5
Polymerization in toluene at 35 ºC, ethylene pressure 2 bar, for 30 min, [Fe] =1.4 х 10 mol/l,
MAO/Fe=500.
* Only oligomers were obtained.
The studied catalysts showed high initial activity that fell with the polymerization time.
In accordance with the previously obtained results [7,9,10], complexes with a single ortho-
substituent on each aryl ring are highly active in oligomerization of ethylene to linear α-
olefines ( Table 2, run 1). The catalysts based on iron complexes with a substituent at both
ortho –positions of the aryl ring in presence of MAO as activator show high activities for
ethylene polymerization, producing strictly linear high-molecular weight polymer. The
molecular weight of the product depends on the size of the alkyl substiuents in 2,6-position of
the aryl rings ( R1, and R2, Scheme 1): with the increase of steric bulk of the substiuents the
Mw values of the produced PE increase. The yield of PE decreases with the increase the
substituents R1 and R2 steric bulk because of lower stability of the catalysts formed (Table 2,
runs 2, 3, Fig 3).
0,8 2
d Wf/ d log[M] 0,4
0,0
2 3 4 5 6 7
Log M
Figure 3. MWD of PE produced with homogeneous catalysts 2,6-R2LFeCl2/MAO: R= Me (2), i-Pr (3),
Cl (4) (Number on the curve corresponds to the number of the experiment in Table 2). ( Wf= weight
fraction, M=molecular weight).
Catalytic system based on the iron complex bearing electron-attracting halogen

substiuents [36] (2,6-Cl2LFeCl2, Table 2, run 4) was found to be less stable, than those
obtained using alkyl-substituted complexes. Though the catalyst (2,6-Cl2LFeCl2/MAO)
exhibited the highest initial activity, the PE yield was lower than that obtained with the
complex 2,6-Me2LFeCl2. Linear PE produced with (2,6-Cl2LFeCl2 /MAO) catalyst was
characterized with the lowest Mw and Mw/Mn values (Table 2, run 4 and Fig 3, curve 4). It
should be mentioned, that introduction of a halogen substituent into the p-position of the aryl
ring results in an increase of the catalysts activity and a decrease in PE Mw value as well
[37]. The obtained results indicate, that besides steric effects, electronic properties of the
substituents in the ligand of iron bis(imino)pyridine complexes have the pronounced
influence upon their polymerization properties.
Characterization of the “Active Species”
The active intermediates of the catalysts based on iron bis(imino)pyridine complexes

with different activators (MAO, AlMe3, Al(i-Bu)3, Al(n-Oct)3) have been studied by 1H , 2H
NMR and EPR spectroscopy [12, 22-28, 38 ]. The authors of [38] reported that upon
interaction of 2,6-Me2LFe(II)Cl2 with the excess of MAO, the intermediates containing iron
in the +3 oxidation state might be formed (however, the question of how iron(II) catalyst
precursors could afford iron(III) catalysts in the presence of such reducing agents as AlMe3
and MAO was not considered). Later on, by a comparative study of 2,6-Me2LFeCl2 /MAO
and 2,6-Me2LFeCl3 /MAO catalysts, it was shown that the close precursors of the active
centers in both catalysts are ferrous complexes containing iron in +2 oxidation state [24].
The structure of the intermediates was determined from 1H and 2H NMR spectra. It has
been reported that in conditions approaching to real polymerization, neutral heterobinuclear
complexes of the type [LMe Fe(II)Cl(μ-R)2AlR2] or [LMe Fe(II)R(μ-R)2AlR2] dominate in the
reaction solution in 2,6-Me2LFeCl2+AlR3 systems, whereas in 2,6-Me2LFeCl2 /MAO systems
the ion pairs [LMeFe(II)(μ-Me)(μ-Cl)AlMe2]+[Me-MAO]- (at Al/Fe< 200) and [LMe Fe(II)(μ-
Me)2AlMe2]+[Me-MAO]- (at Al/Fe> 500) were the predominant species [24-27].
Activation of 2,6-i-Pr2LFeCl2 with MAO and aluminium trialkyls ( AlMe3, Al(i-Bu)3) has
been studied in more details using 1H and EPR spectroscopy [28]. It was found that
interaction of 2,6-i-Pr2LFe(II)Cl2 with aluminium trialkyls results in one-electron reduction of
the former with formation of heterobinuclear complex of the type [LiPr(-)Fe(+)(μ-Me)2AlMe)2]
or [LiPr(-)Fe(+)(μ-i-Bu)(μ-X)Al(i-Bu)2] (X = i-Bu or Cl), depending on the activator used
(either AlMe3 or Al(i-Bu)3). The observed intermediates were relatively unstable and decayed
within minutes at room temperature. At the same time, formation of new EPR active species
was observed: (1) LiPrAlMe2 having signal at g = 2.003 and (2) another species with a signal
at g = 2.08, presumably of the type L′FeI-Alk where the modified ligand L′ has a singlet
ground spin state and iron (I) is low-spin (S = 1/2). When “AlMe3-free” methylalumoxane
(MAO (50)) was used as the activator, ion pairs of the type [LFeII(μ-Me)2AlMe2]+[MeMAO]−
are formed. These ion-pair intermediates are more stable and persist in solution for several
hours.
Data on the Number of Active Centers and Propagation Rate Constants
The data on the number of active centers (Cp) and rate constants of propagation reactions
(kP) at olefin polymerization with homogeneous catalysts are of great importance for analysis
of the kinetic peculiarities of the reaction and elucidation of factors, determining the catalysts
activity. Polymerization inhibition by 14CO is a well known method for the determination of
the active metal-carbon bonds in the catalytic systems of different types. This method is based
on 14CO insertion into the metal-polymer bond, thus causing termination of the
polymerization process and formation of labeled polymer. Earlier we have used this method
to evaluate CP and kP values for ethylene and propylene polymerization with Ziegler-Natta
catalysts [39,40]. As it was shown in [41], carbon monoxide reacts with a Fe(II)-complex of
composition С5H5(CO)2Fe(CH3) by inserting into the Fe-CH3 bond. A variety of alkyl
complexes of transition metals react with carbon monoxide in the same manner. The available
literature data on the reaction of carbon monoxide with a Fe(II) alkyl complexes prove
feasible application of polymerization inhibition with 14CO for determination of the Fe-
polymer chains number (number of active centers) at polymerization over the catalysts based
on bis(imino)pyridine complexes of Fe(II). Thus, we have used this method to determine the
СР and kP values at ethylene polymerization over (2,6-Me2LFeCl2/MAO) and (2,6-
Me2LFeCl2/Al(i-Bu)3) catalysts [30-32].
The obtained СР and kP values are summarized in Table 3. The СР values determined at
short polymerization times (τpol = 1.5-2 min) were equal to 0.07 and 0.41 mol/mol Fe for 2,6-
Me2LFeCl2/МАО and 2,6-Me2LFeCl2/Al(i-Bu)3 catalysts, respectively (Table 3, runs 1 and
3). For both catalysts the CP values decrease with polymerization time. At the initial period of
polymerization the reactivity of the examined catalysts (especially 2,6-Me2LFeCl2/MAO) is
extremely high (kP = 5×104 L/mol·s at 35ºC), for comparison, the kP value of the Ziegler-type
catalyst TiCl4/MgCl2/AlEt3 is equal to 1.2×104 L/mol·s at 80ºC [42-44]. For both catalyst 2,6-
Me2LFeCl2/MAO ( Table 3, runs 1 and 2) and 2,6-Me2LFeCl2/Al(i-Bu)3 (Table 3, runs 3 and
4) the kP value observed at τpol = 1.5 – 2 min noticeably decreases as the reaction proceeds.
Table 3. CP, kP and PE MWD data obtained at ethylene polymerization over the
catalysts based on 2,6-Me2LFeCl2
Run Cocatalyst τpol, R2), CP, kР,

1) Mw Mw/Mn
min. Kg PE/ mol Fe mol/mol Fe L/mol s
× 10-3
bar min
1 MAO 1.5 600 0.076 49500 44 6.9
2 – // – 9 100 0.039 15000 54 7.2
3 Al(i-Bu)3 2 1700 0.41 26000 39 7.6
4 – // – 7 210 0.16 8200 66 7.1

1)
Polymerization in toluene ( runs 1,2) or heptane ( runs 3,4) at 35 ºC, ethylene pressure 2.9 bar,
[Fe] = 3-8×10 -6 mol/l, Al/Fe = 500; 14CO/Fe = 21; τCO = 5 min.
2)
Polymerization rate in the moment of 14СО introduction.
Thus, deactivation of 2,6-Me2LFeCl2/МАО and 2,6-Me2LFeCl2/Al(i-Bu)3 catalysts with

polymerization time is determined both by lowering of the active centers number and the
decrease of the calculated kP value.
0,8 9 min 0,8 b)

a)
0,6 7 min
0,6
d Wf / d log M
d Wf / d log M
1.5 min 2 min

0,4 0,4
0,2 0,2
0,0 0,0
2 3 4 5 6 7 2 3 4 5 6 7
log M log M
Figure 4. Effect of polymerization duration on the MWD of PE produced with 2,6-Me2FeCl2/MAO.

(Table 3; runs 1 and 2) ( a) and 2,6-Me2FeCl2/Al(i-Bu)3 catalysts (Table 3; runs 3 and 4) (b).
The data presented above allow to suggest that active centers with different reactivity
(i.e., with different kP value) are presented in both catalysts 2,6-Me2LFeCl2/МАО and 2,6-
Me2LFeCl2/Al(i-Bu)3. As polymerization proceeds, the centers with high reactivity in the
chain propagation reaction are deactivated first. Data on the broad and bimodal MWD of PE,
produced at polymerization over these catalysts (Fig.4) confirm the conclusion on the
formation of active centers with different reactivity [30].
The data of Fig. 4 show that contribution of the low-molecular-weight shoulder in MWD
curves decreases with the increasing of polymerization time. The detailed analysis of MWD
data [32] draw us to the conclusion that at τpol = 1-10 min two types of active centers are
present in the studied catalysts. At the initial stage of polymerization, highly active but
unstable centers produce the low molecular weight PE. The less active and more stable
centers produce PE with high Mw. The ratio of different centers changes with polymerization
time. As apparent from the above, the values of propagation reaction rate constants calculated
for ethylene polymerization over 2,6-Me2LFeCl2/МАО and 2,6-Me2LFeCl2/Al(i-Bu)3
catalysts are the average values, characterizing different active centers present in the system
at the time moment. We believe, that at the starting moment of polymerization (τрol < 1.5
min), the proportion of highly active centers is higher and, correspondently, the values of kP
should be higher then the measured average values 5-2.6×104 L/mol⋅s. It should be noted that
the increase in PE molecular weight with polymerization time going with simultaneous
reduction of the average kP values indicate a sharp decrease in the average rate of chain
transfer reactions. This lowering is faster than the decrease of the rate of chain propagation.
Thus, the main peculiarities of iron bis(imino)pyridine complexes as an active component
of the homogeneous ethylene polymerization catalyst are the following: 1) high activity at
activation with different organoaluminium activators and especially with aluminium trialkyls;
2) formation of linear PE with high Mw and broad MWD; 3) noticeable effect of the size and
the nature of the substituents at 2,6 –positions of the aryl ring in the ligand of iron complex
and of the organoaluminium activator on the Mw and polidispersity (Mw/Mn values) of the
resulted PE; 4) formation of the multiple active sites (differing by reactivity and stability in
the chain propagation and transfer reactions) in these catalysts upon interaction of RnLFeCl2
with both MAO and aluminium trialkyls and variation of the ratio of these sites in course of
polymerization; 5) presence of active centers with very high kp value (≥ 5.0×104 L/mol s,
350C), but low thermal stability; 6) strong effect of catalysts composition and polymerization
duration upon the number of active centers; the measured Cp values vary in the range of 0.41-
0.04 mol/mol Fe.
2.2 CATALYSTS BASED ON RNLCOCL2

Effect of Activators
Table 4 presents the data on the catalytic activity at ethylene polymerization of the Co(II)
bis(imino)pyridine complex (2,6-Me2LCoCl2) with different activators and characteristics of
the obtained PE samples. The results of Table 4 (runs 1-3) show that, when activated with the
same co-catalysts, 2,6-Me2LCoCl2 exhibited noticeably lower activity than the analogous
Fe(II) bis(imino)pyridine complex (Table 1, runs 1,2,4).
The catalyst system 2,6-Me2LCoCl2/Al(i-Bu)3 was almost inactive (Table 4, run 4).
Like the 2,6-Me2LFeCl2-based systems, catalysts with 2,6-Me2LCoCl2 as the active
component were inactive at polymerization temperatures above 50ºC. The time-dependent

polymerization activities of the catalysts based on 2,6-Me2LCoCl2 are shown in Fig. 5.
Table 4. Ethylene polymerization over the catalysts based on 2,6-Me2L Cl2
3) 4)
Run Activator Yield Maximum Mw Mw/ Content Content per PE
Kg PE/ activity, Mn per 1000 С molecule
×
mol Co bar
Kg PE/ mol 10-3
Co bar min СН3 СН= СН3 СН=
СН2 СН2
11) MAO 3100 75 1.5 1.8 15.0 15.0 0.9 0.9
21) MAO 2700 100 1.9 1.9 16.0 16.8 1.1 1.2
(50)
31) AlMe3 3600 60 1.6 1.8 16 16 1.0 1.0
42) Al(i-Bu)3 20 10 - - - - - -
1)
Polymerization in toluene at 35 ºC, ethylene pressure 5 bar, for 30 min, [Co] =1.4×10-5 mol/l,
Al/Co=500.
2)
Polymerization in heptane, all other conditions were as in runs 1-3
3)
4) 13
C NMR data
100
1
Activity, kg PE/ mol Co bar min
80
3
60
40 2
20
0
10 20 30
Time, min
Figure 5. Kinetic curves for ethylene polymerization over the catalysts composed of 2,6-Me2LCoCl2
and different activators: (1) - MAO; (2) - МАО(50); (3) - AlMe3. (Number on the curve corresponds to
the number of the experiment in Table 4).
As in the case of bis(imino)pyridine iron complexes, the catalysts 2,6-Me2LCoCl2 /MAO

(MAO(50)) demonstrate high initial activity that fell with the increase in polymerization time.
The values of the initial activity and the rate of deactivation depend on the activator
composition. Similar to 2,6-Me2LFeCl2, 2,6-Me2LCoCl2 activated by MAO demonstrates
high initial activity and the highest deactivation rate (Table 4, run 1, Fig. 5, curve 1). The
catalyst formed by interaction of cobalt complex with AlMe3 was characterized with
noticeably higher stability ( Fig. 5, curve 3).
The PE samples obtained with homogeneous catalysts composed of 2,6-Me2LCoCl2 and
different activators are characterized by low Mw and narrow MWD (Mw/Mn=1.8-1.9, Table
4). These polymers are extremely linear, containing one terminal –CH3 and one –CH=CH2
group per polymer molecule (Table 4). Thus, at interaction of 2,6-Me2LCoCl2 with different
activators only one type of active center is formed, and in contrast to 2,6-Me2LFeCl2, the
homogeneous catalysts based on this cobalt complex can be regarded as the single-site
catalysts.
Effect of the Ligand Composition
The data about ethylene polymerization over Co bis(imino)pyridine complexes bearing

different alkyl substiuents in the aryl rings of the ligand activated with MAO are presented in
Table 5 and Fig. 6.
Table 5. Effect of the substituents R on the activity of Rn-LCoCl2/MAO catalysts and

produced PE molecular weight characteristics
1)
Run Rn Yield Maximum activity, Mw Mw/Mn
Kg PE/ mol Co bar × 10-3
Kg PE/ mol Co bar min
1 2,6-Me2 2900 280 1.5 1.8
2 2,4,6-Me3 5800 700 1.7 1.8
3 2,6 -i-Pr2 1250 150 18 2.0
4 2-t-Bu 4500 750 330 2.5
2)
5 2,5-t-Bu2 6100 270 1200 -
Polymerization in toluene at 35 ºC, ethylene pressure 2 bar, for 30 min ( for run 1 - 15 min) ,
[Co] =1.4 х 10 -5 mol/l, MAO/Co=500.
1)
2)
Mv value (intrinsic viscosity data)
The values of maximum activity and the rate of catalysts deactivation depend on the
ligand composition of cobalt complexes. In comparison with 2,6-Me2LCoCl2 /MAO system,
the catalyst based on 2,4,6-Me3LCoCl2 complex, bearing three Me groups in o- and p-
positions of the aryl rings, demonstrates higher initial activity, causing the increased yield of
PE ( Table 5, runs 1 and 2, Fig 6, curves 1 and 2). In accordance with the literature data [10,
45-47], the catalyst 2-t-Bu-LCoCl2/MAO was less stable, its high initial activity sharply fell
within some minutes ( Fig. 6, curve 4), whereas the system based on 2,5-t-Bu2LCoCl2
displayed quite stable kinetic curve, resulting in the highest PE yield (Table 5, run 5, Fig 6,
curve 5).
PE samples obtained with the catalysts RnLCoCl2/MAO were characterized with narrow
MWD ( Mw/Mn=1.8-2.5) and high linearity ( one terminal -CH3 and one -CH=CH2 group per
polymer molecule) ( Table 5). Introduction of the third alkyl substituent into the p- position of
the aryl ring had almost no effect on the Mw and polydispersity values of PE ( Table 5, runs 1
and 2). The value of PE molecular weight noticeably increased with the increasing steric bulk
of the substiuents R ( Table 5, runs 1, 3, 5). The catalyst based on 2-t-Bu-LCoCl2, bearing the
only one t-Bu -group in o-position of the aryl ring, produced PE with the Mw value more than
200 times higher than that of polymer, obtained over 2,6-Me2LCoCl2 /MAO catalyst (Table 5,
Runs 1 and 4). Introduction of the second t-Bu-group into the ligand results in formation of
PE with extremely high molecular weight ( Mv = 1200000, Run 5). Cobalt complexes with
halogen substituents are approximately an order of magnitude less active than their iron
analogues and produce linear PE with very low Mw and narrow Mw/Mn ( for PE produced
with 2,6-Cl2LCoCl2 at 00C Mw=370 g/mol, Mw/Mn= 1.15) [36].
Activity, kg of PE/ mol Co min bar
800
600
1 2 4
5
400
200
10 20 30
Time, min
Figure 6. Kinetic curves for ethylene polymerization over homogeneous catalysts Rn-PhLCoCl2/MAO:
Rn= 2,6-Me2 (1), 2,4,6- Me3 (2), 2-t-Bu (4), 2,5-t-Bu2 (5). (Number on the curve corresponds to the
number of the experiment in Table 5).
Thus, similar to the iron complexes, ligand environment in bis(imino)pyridine cobalt

complexes has a great influence on theirs polymerization behavior (activity, stability and MW
of the produced PE). It should be noted, that narrow MWD of all obtained PE samples
indicate that independently of their ligand composition, the catalysts based on
bis(imino)pyridine cobalt complexes retain their single-site character.
Characterization of the “Active Species”
Recently the nature of the active sites of polymerization formed upon interaction of
bis(imino)pyridine cobalt complexes with MAO and aluminium trialkyls was intensively
studied [12, 40-42]. According to results of Gibson and Gal, in the LCoIICl2/MAO system,
initial cobalt(II) pre-catalyst reduction to cobalt(I) halide is followed by conversion to a
cobalt(I) methyl and ultimately to a cobalt(I) cationic species. Addition of ethylene affords an
ethylene adduct [LCoI(η2-C2H4)]+[Me-MAO]−, which is considered as the immediate
precursor to the active species [48-50] In contrast, our 1H and 2H NMR studies of 2,6-
Me2LCoIICl2/MAO system showed that cobalt(II) complex with proposed structure 2,6-
Me2LCoIIMe(Cl)(MAO) strongly predominates in the reaction solution at 20°C for at least
several hours after mixing 2,6-Me2LCoIICl2 and MAO [12 ].
The detailed 1H, 2H, and 19F NMR characterization of cobalt(II) and cobalt(I) species
formed in the systems Rn-LCoIICl2/MAO, LCoIICl2/AlMe3/[CPh3][B(C6F5)4] and
LCoIICl2/AlMe3 (where Rn = 2,6-Me2, 2,4,6-Me3-, 2,6-i-Pr2 and 2-t-Bu) was recently
undertaken [29]. It was shown, that the ion pairs [RnLCoII(μ-Me)2AlMe2]+[A]−,
[RnLCoIIMe(S)]+[A]−, and [RnLCoI(S)]+[A]− can be observed in the catalyst systems
RnLCoIICl2/MAO and RnLCoIICl2/AlMe3/[CPh3][B(C6F5)4] ([A]− = [Me-MAO]− or
[B(C6F5)4]−; S = toluene or vacancy), whereas neutral complexes RnLCoI(μ-Me)(μ-Cl)AlMe2
and RnLCoI(μ-Me)2AlMe2 predominate in the catalyst systems RnLCoIICl2/AlMe3. Addition
of monomer (C2H4) plays the key role in formation of the direct precursors of the
polymerization active centers of the catalysts based on RnLCoIICl2. In the case of
RnLCoIICl2/MAO systems, addition of ethylene results in the rapid reduction of cobalt(II) to
cobalt(I) and only the ion pairs of the type [RnLCoI(S)]+[A]− are present in the reaction
solution at 20°C. In the case of RnLCoIICl2/AlMe3 systems, in the presence of ethylene the ion
pair with proposed structure [RnLCoI(η2-C2H4)]+[AlMe3Cl]− is the major cobalt species in the
reaction solution. Thus, in contrast to the catalysts based on bis(imino)pyridine complexes of
iron, similar intermediates (ion pairs of cobalt(I)) are present in the systems
RnLCoIICl2/MAO/C2H4 and RnLCoIICl2/AlMe3/C2H4. The obtained results can explain the
close polymerization results (similar activity and PE structure) obtained with the catalyst
systems formed by interaction of RnLCoCl2 complexes with MAO and AlMe3.
Data on the values of Cp and kP at ethylene polymerization with the catalysts 2,6-
Me2LCoCl2/MAO have been obtained by method of polymerization quenching by 14 CO [33,
34]. We have to extend this study to polymerization over the catalysts based on 2-t-BuLCoCl2
and 2,5-t-BuLCoCl2 complexes. The obtained data are summarized in Table 6.
In the initial moment of polymerization over the catalyst 2,6-Me2LCoCl2/MAO the
number of active centers is high ( 23% with respect to total content of cobalt complex) (
Table 6, run.1). With the increase in polymerization time form 5 to 15 min, the CP value
decreases by a factor of 1.6 ( up to 0.14 mol/mol Co, Table 6, run 2). In contrast to the
catalysts based on 2,6-Me2LFeCl2, the values of propagation rate constant determined for the
catalyst 2,6-Me2LCoCl2/MAO ( 3.6×103 L/mol⋅s at 350С) were independent of the reaction
time. Obviously, the reason of the catalyst 2,6-Me2LCoCl2/MAO deactivation with the
increase of polymerization time is the reducing of the active centers number. It should be
mentioned that the number of active centers formed in the system 2,6-Me2LCoCl2/MAO (23-
14% with respect to total content of cobalt complex) is noticeably higher than that formed in
2,6-Me2LFeCl2/MAO catalyst (8-4%, Table 3). The reduced polymerization activity of the
catalyst 2,6-Me2LCoCl2/MAO in comparison with that of the catalyst based on iron complex
is determined by lower propagation rate constants.
Table 6. CP, kP and PE MWD data at ethylene polymerization over the catalysts Rn-
LCoCl2/MAO.
Run Complex τpol, R2), CP, kР, k trM ,

1) Mw Mw/Mn
min Kg PE/ mol mol/ L/mol s
L/mol s × 10-3
Co bar min mol Co
1 2,6-Me2LCoCl2 5 130 0.23 3520 90 1.9 1.7
2 – // – 15 80 0.14 3570 100 1.8 1.8
3 2- t-BuLCoCl2 1 520 0.73 3580 0.82 320 2.7
2,5-t- -
4 3.5 210 0.48 2350 - -
Bu2LCoCl2
2,5-t-
53) 3.5 270 0.69 3200 0.53) 3703) 2.13)
Bu2LCoCl2
1)
Polymerization in toluene at 35 ºC, ethylene pressure 2.9 bar, [Co] =5 - 16×10-6 mol/l, Al/Co=500;
14
CO/Co = 13-40; τCO = 5 min..
2)
3)
Polymerization at 500C
The data of Table 6 show that PE samples, obtained with 2,6-Me2LCoCl2/MAO at

different polymerization time (5- 15 min), are characterized by similar Mw, Mw/Mn and kP
values. So, in contrast to the catalysts based on the corresponding iron complex, were a set of
active centers is formed and the determined kP is an average value ( Table 3), the catalyst 2,6-
Me2LCoCl2/MAO contains only one type of active center and the determined kP value reflects
the actual reactivity of these centers.
The values of propagation rate constant determined for 2-t-BuLCoCl2 /MAO and 2,5-t-
BuLCoCl2/ MAO catalysts were close to that, found for 2,6-Me2LCoCl2/MAO system (Table
6, runs 3, 4). Evidently, higher activities of the systems based on t-Bu-substituted complexes
in comparison with that of the catalyst 2,6-Me2LCoCl2/MAO, are accounted for higher
numbers of the active centers present in these systems (0.23, 0.48 and 0.73 mol/molCo
correspondingly for Me2LCoCl2 , 2-t-BuLCoCl2 and 2,5-t-Bu2 LCoCl2, Table 6)
Study on the effect of the monomer pressure (1-5 bar) upon the molecular weight
characteristics of the PE, produced with RnLCoCl2/MAO catalysts (Rn = 2,6-Me2-, 2,4,6-Me3-
2-t-Bu-, 2,5-t-Bu2-), have shown that Mw and Mw/Mn values of polymers are independent of
the monomer pressure. The obtained PE samples were highly linear and contain one –CH3
and one –CH=CH2 group per polymer chain. These results provide evidence, that the main
reaction of polymer chain transfer at polymerization over these catalysts is the reaction of the
chain transfer to monomer. On the basis of the obtained experimental data the values of chain
transfer rate constants (ktrM ) were determined (Table 6). The value of ktrM depends on the
steric bulk of the o-substiuents in the aryl ring of the ligand (ktrM = 90 and 0,82 L/mol s for
2,6-Me2LCoCl2 and 2-t-BuLCoCl2 correspondingly, polymerization at 350C, Table 6, runs 1
and 3). The value of ktrM for 2,5-t-Bu2 LCoCl2 – based catalyst was found to be 0.5 L/mol s
(polymerization at 500C). Bulky substituents at the o-position of the aryl ring of complex
ligand hinder the reaction of chain transfer, and with the increase of the substituents bulk the
value of ktrM decreases, thus leading to the increase in the molecular weight of the produced
PE.
Thus, cobalt bis(imino)pyridine complexes as ethylene polymerization catalysts are
characterized by reduced activity in comparison with that of corresponding RnL2FeCl2
complexes. This low activity is determined by lower value of rate propagation constants. The
catalysts formed by interaction of RnLCoCl2 with both MAO and aluminium trialkyls are
single-site systems; they produce highly linear PE with narrow MWD. The bulk of the
substituents at the o –positions of the aryl ring in the ligand of cobalt complex greatly affects
the activity and the Mw values of the PE produced. It was found that the increased activity of
complexes with t-Bu-substituents is determined by an increase in the number of active centers
with the same kP value. Increase of PE molecular weight is determined by strong decrease in
the value of chain transfer rate constant.
2.3. CATALYSTS BASED ON RNLVCL3

Bis(imino)pyridine complexes of V(III) as active catalysts for ethylene oligomerization
and polymerization were introduced by R. Schmidt et.al. [18]. In presence of MAO as
activator productivities of vanadium complexes varied from 3×103 to 580×103 kg PE/mol V
for 30 min at reaction temperature 600C and ethylene pressure 250 psig. The catalysts
productivity and properties of the obtained products depend on the substituents in the aryl
ring of bis(imino)pyridyl ligand : as the bulk of the alkyl substituents increases, the
productivity decreases, whereas formation of solid PE increases. Products obtained with 2,6-
substituted complexes consisted mainly of solid polymer.
Effects of Polymerization Temperature and Activators
2,6-Et2LV(III)Cl3 was used to study the effects of polymerization temperature and

activators upon the catalysts properties at ethylene polymerization. The obtained results are
collected in Table 7 and Fig. 7.
In contrast to the iron and cobalt-based catalysts, inactive at polymerization temperatures
above 50 ºC, catalytic systems based on 2,6-Et2LVCl3 were highly active at 60 ºC (Table 7,
runs 1 and 3). At 35ºC, 2,6-Et2LVCl3 activated with commercial MAO, was characterized by
lower activity but the stable kinetic curve (Fig. 7, curve 1).
Table 7. Ethylene polymerization over the catalysts based on 2,6 Et2LVCl3
2)
Run Activator T
τpol, 1)
Yield
Maximum
Mw Mw/Mn 3)
Content per 1000 С Content per PE
min activity,
°C -3 molecule
Kg PE/ mol × 10
Kg PE/ mol V
V bar
bar min СН3 СН=СН2 СН3 СН=СН2
1 MAO 35 30 3300 170 6.7 2.4 - - ‐ ‐
2 MAO 60 4 3250 350 5 2.1 - - ‐ ‐
3 MAO 60 30 11000 360 12 4.8 4.2 4.2 1.0 1.0
4)
4 MAO(20) 60 30 6500 260 - - - - - -
1) -5
Polymerization in toluene at ethylene pressure 2 bar, [V] =1.4 ×10 mol/l, Al/V=500.
2)
3) 13
C NMR data
4)
MAO sample with reduced content of AlMe3 (~ 0.01 M of AlMe3)
400
Activity, kg PE/ mol V bar min

300
3
200
100 1
0
10 20 30
Time, min
Figure 7. Kinetic curves of ethylene polymerization over 2,6-Et2LVCl3 /MAO . (1) –polymerization at
35 °C; (3) – polymerization at 60 °. (Number on the curve corresponds to the number of the experiment
in Table 7).
In polymerization runs at 60 ºC the catalyst 2,6-Et2-LVCl3/MAO showed high initial

activity (Fig. 7, curve 3). which rapidly fell with the polymerization time. Reducing the free
AlMe3 content in MAO samples (MAO(20)) used for activation of vanadium complex (Table
7, run 4) led to the decrease of the initial activity and of the PE yield. In the presence of MAO
completely purified from free AlMe3 (MAO(50)) or with AlMe3 as activator, 2,6-Et2LVCl3
was inactive.
PE prepared with the catalysts 2,6-Et2LVCl3 /MAO) displayed high linearity and low
Mw. (Table 7). The value of PE polydispersity depends on the polymerization conditions
(temperature and polymerization time). PE with narrow MWD (Mw/Mn =2.4) was obtained
in polymerization run at 35 ºC (Table 7, run 1). Increase in the polymerization temperature up
to 60 ºC resulted in formation of PE with narrow MWD at short polymerization time
(Mw/Mn=2.1, at τpol = 4min; Table 7, run 2), but with the increase in polymerization times
polydispersity of PE increases (Table 7, run 3, Mw/Mn=4.8). Evidently, interaction of 2,6-
Et2LVCl3 with MAO at the temperature 600C generates unstable centers of the only one type.
These centers are responsible for the formation of PE with low Mw and narrow MWD at the
beginning of polymerization. As the polymerization proceeds, the new centers which produce
PE with higher Mw are formed. As a result, Mw and Mw/Mn values of the produced PE
increase with time.
The nature of the active species formed upon interaction of RnLVCl3 with MAO remains
unclear. The samples (2,6-Et2LVCl3 +MAO) display broad unresolved NMR and EPR spectra
that hinder the assignment of the signals.
The method of polymerization quenching by 14CO was applied to determine the Cp and
kP values for ethylene polymerization over the catalysts 2,6-Et2LVCl3 /MAO and 2,6-
Me2LVCl3 /MAO at 35 and 600C. The obtained results are shown in Table 8.
Table 8. CP, kP and PE MWD data at ethylene polymerization over the catalysts
based on 2,6 R2LVCl3 complexes
Run.1) Complex T, τpol, R2), CP, kР, Mw, Mw/Mn

0
C min Kg PE/ mol V mol L/ mol V s × 10-3
bar min /mol V
2,6-
1 35 5 90 0.18 2580 5.7 2.5
Et2LVCl3
2 – // – 60 2 870 0.50 16430 5.5 2.2
3 – // – 60 19 210 0.31 6380 11 4.1
2,6- 880 0.42 19900

4 60 3 3.3 1.9
Me2LVCl3
1)
Polymerization in toluene at ethylene pressure 2.9 bar, [V] =14 - 21 ×10-6 mol/l, Al/V=500,
МАО/V = 500-700; 14CO/V = 14-22; τCO = 5 min.
2)
The values of Cp and kP found for 2,6-Et2LVCl3 /MAO catalyst at 350C ( Table 8, run1)
are lower than those for the catalysts, based on iron and cobalt bis(imino)pyridine complexes
(Tables 3 and 6), being the reason of the lower activity of 2,6-Et2LVCl3 /MAO at this
temperature. With the increase in polymerization temperature up to 60oC, activity of the
vanadium based catalysts noticeably increases due to the increase in both the active centers
number and kP value ( Table 8, runs 1 and 2). Similar activity exhibited by the catalysts based
on 2,6-Et2LVCl3 and 2,6-Me2LVCl3 is determined by formation of close number of active
centers (Cp = 0.4-0.5 mol/mol V) with similar reactivity (kP = 1.6-2.0×104 L/mol s) (Table 8,
runs 2 and 4).
The molecular weight of the polymers, obtained with vanadium bis(imino)pyridine
complexes, depend on the steric bulk of the substituents in 2,6-position of the aryl rings of the
ligand. MW of PE produced with 2,6-Et2LVCl3/MAO catalyst is somewhat higher than that
of polymer, prepared using the system based on 2,6-Me2LVCl3 ( Table 8, runs 2 and 4 and
Fig. 8, curves 1 and 3). In both cases PE with narrow MWD (Mw/Mn = 1.9 – 2.2) was
obtained, indicating that at activation of vanadium bis(imino)pyridine complexes with MAO
only one type of active centers is generated.
2
1,2
4
1,0
0,8
d Wf / d log M
0,6
0,4
3
0,2
0,0
1 2 3 4 5 6 7
log M
Figure 8. MWD of PE produced over RnLVCl3/MAO catalysts at 600C: (2) Rn = 2,6-Et2-,

polymerization for 2 min; (3) Rn = 2,6-Et2-, polymerization for 19 min; (4) Rn = 2,6-Me2-,
polymerization for 3 min; (Number on the curve corresponds to the number of the experiment in Table
8).
Effect of the reaction time upon the Cp and kp values at polymerization over the catalyst
2,6-Et2LVCl3/MAO was studied ( Table 8, runs 2 and 3). As polymerization proceeds from 2
to 20 min, the catalyst activity noticeably decreases. It was found that deactivation of the
catalyst with polymerization time is caused by lowering of both the number of active centers
and the value of propagation rate constant.
PE sample obtained at longer polymerization time was characterized by the increased
Mw value and broadened MWD due to formation of a high-molecular weight PE fraction (
Fig. 8, curve 2). Probably, at longer polymerization times new active centers, producing high
molecular weight PE appear in the system and initially single-site catalyst 2,6-
Et2LVCl3/MAO should then be regarded as a multi-site one. In this case (Table 8, run 3), the
determined reaction rate constant is an average value, characterizing different active centers
present in the system at the time moment.
Thus, vanadium bis(imino)pyridine complexes are effectively activated only with MAO
Reduction of the free AlMe3 content in MAO reduces the catalytic activity of RnLVCl3/MAO
system. Active centers formed by interaction of RnLVCl3with MAO demonstrate higher
thermal stability in comparison with those of RnL2FeCl2 and RnLCoCl2–based systems. The
catalysts RnLVCl3/MAO act as a single-site systems at low polymerization temperatures
(35°C). At high temperature (60 °C) they act as a single-site catalysts only at a short
polymerization times, but as the polymerization proceeds they turn into multi-site catalysts.
2.4. Catalysts Based on RnLCrCl3
A family of chromium (III) bis(inino)pyridine complexes (RnLCrCl3, Rn= H, Me, Et, i-Pr,
t-Bu) was synthesized and tested in ethylene polymerization by Esteruelas et.al [19]. It was
shown that upon activation of RnLCrCl3 with MAO the catalysts highly active at the increased
polymerization temperatures (700C) are formed. These catalysts produce highly linear
polyethylene. The substituents at the o-position of the N-aryl groups affected both catalytic
activity and molecular weight of the resulting PE. Complexes with two o-substituents proved
to be more active catalysts than those, bearing one alkyl group in the o- position of the aryl
ring. The increase of steric bulk of the substituents causes a decrease in the catalytic activity,
whereas the molecular weight of the produced PE increases. The highest activities were
achieved with the catalysts based on Cr(III) complex with Me substituents in both o- and p-
position of the aryl ring (2,4,6-Me3LCrCl3 ).
Effect of Activators
Figure 9 (curve 1) shows the kinetic curve of the ethylene polymerization at 70°C over
chromium(III) bis(imino)pyridine complex (2,4,6-Me3LCrCl3) activated with MAO. In
contrast to the previously described catalysts based on iron, cobalt and vanadium complexes,
and in line with the results of ref. [19], at polymerization with this catalyst a long period of
acceleration is observed.
The effective method to form the active component of these catalysts via preliminary
interaction of 2,4,6-Me3LCrCl3 with MAO solution at low molar ratio of the components
(AlMAO/Cr=100-200) was suggested in ref. [19]. A thus prepared solution of the chromium
complex is very stable and could be used for ethylene polymerization at 70 °C in heptane
with Al(i-Bu)3 as an additional co-catalyst.
400
2
Activity, kg PE/mol Cr bar min
4
300
6
200
1
100
0
10 20 30 40 50 60
Time, min
Figure. 9. Kinetic curves for ethylene polymerization over 2,4,6-Me3LCrCl3 at various preactivation
mode and polymerization temperature: (1) - polymerization without preactivation ( polymerization at
70 °C and 5 bar of C2H4 , in toluene with MAO as co-catalyst, Al/MAO=500). (2) - preactivation with
MAO at 250C, MAO/Cr= 200 ( polymerization at 70 °C, in heptane, at 5 bar of C2H4, with Al(i-Bu)3 ,
Al(i-Bu)3 /Cr=1000); (4) - preactivation with MAO (50) at 250C, MAO/Cr= 200 ( polymerization at 70
°C, in heptane, at 5 bar of C2H4, with Al(i-Bu)3, Al(i-Bu)3 /Cr=1000); (6) - preactivation with MAO at
250C, MAO/Cr= 200 ( polymerization at 35 °C, in heptane, at 5 bar of C2H4, with Al(i-Bu)3, Al(i-Bu)3
/Cr=1000); (Number on the curve corresponds to the number of the experiment in Table 9).
Table 9. Effect of preactivation mode on the ethylene polymerization activity of 2,4,6-Me3LCrCl3
5)
4) Maximum 6)
Run. Pre-activator [Cr] Yield Mw Mw/Mn Content per 1000 С Content per PE
activity,
Kg PE/ mol × 10-3 molecule
µmol/l
Cr bar Kg PE/ mol Cr bar
min СН3 СН=СН СН3 СН=СН
2 2
11) - 20.0 4740 140 1.3 1.9 - - - -
22) MAO 3.3 7880 330 1.5 1.9 17.0 15.6 0.97 0.9
32) MAO (20) 5.0 9680 400 - - - - - -
42) MAO (50) 5.0 9920 360 1.2 1.7 17.2 16.0 0.9 0.8
52) MMAO 5.0 2870 300 - - - - - -

63) MAO 5.0 12400 260 1.1 1.9 - - - -
1)
Polymerization in toluene at 70ºC, ethylene pressure 5 bar, for 60 min, co-catalyst MAO (AlМАО/Cr=500)
2)
Polymerization in heptane at 70ºC, ethylene pressure 5 bar, for 30 min, co-catalyst Al(i-Bu)3
(Al(i-Bu)3/Cr =1000),
3)
Polymerization at 35ºC, ethylene pressure 5 bar, for 30 min, co-catalyst Al(i-Bu)3
(Al(i-Bu)3/Cr=1000),
4)
Molar ratio Al/Cr =200
5)
6) 13
C NMR data
In the case of pre-activation of 2,4,6-Me3LCrCl3 with MAO at the molar ratio AlMAO/Cr
=200, the polymerization starts immediately with high activity (Fig. 9, curve 2) providing
higher PE yield in comparison with that of the system without preactivation (Table 9, runs 1
and 3).
The EPR studies of the catalyst systems 2,4,6-Me3LCrCl3/activator (where activator was
MAO, MMAO) have shown the appearance of EPR spectra after mixing the reagents. These
spectra are characteristic of S = 3/2 chromium(III) complexes [51]. The initial signals of
Cr(III) disappeared within 5-30 min, depending on the nature of the co-catalyst used.
Apparently, the activation of 2,4,6-Me3LCrCl3 with MAO leads to formation of the active
centers via the reduction of Cr(III) to a lower oxidation state. In accordance with that,
recently synthesized bis(imino)pyridine complexes of Cr (II) [52] and complexes containing
Cr in formal monovalent oxidation state [53] proved to be highly active at ethylene
polymerization in the presence of MAO.
Data in Table 9 and Fig. 9 show that the preactivated systems 2,4,6-Me3
LCrCl3/MAO/Al(i-Bu)3 revealed high initial activity at increased polymerization temperature
(70 ºC ) which rapidly fell with the increase in polymerization time. Therefore the yield of PE
obtained in polymerization run at 35 ºC for 30 min was 1.5 times higher than that, obtained in
polymerization at 70 ºC (compare runs 2 and 6, Table 9) due to the higher stability of the
catalyst at lower polymerization temperature. (Figure 9, curves 2 and 6). Catalytic systems
based on 2,4,6-Me3LCrCl3, preactivated by different samples of MAO produce highly linear
PE with narrow MWD (Mw/Mn = 1.7÷1.9) and close Mw values (1.2÷1.5×103) (Table 9,
runs 2-4).
Table 10 represents the data on the number of active centers and their reactivity for
ethylene polymerization at 35 and 700C with 2,4,6-Me3LCrCl3/MAO/Al(i-Bu)3 catalyst,
determined using the method of polymerization quenching by 14CO.
At 350C and at a short polymerization time (τpol = 4 min) the number of active centers
formed in the catalytic system is rather high ( 0.36 mol/mol Cr), whereas the reactivity of
these centers is relatively low ( (kp= 1400 L/mol s, Table 10, run 1). The Cp value determined
at the increased polymerization temperature (700C , τpol= 3,5 min) was noticeably higher (Cp=
0.76 mol/mol Cr). With the increase in polymerization temperature the kP value also increases
up to 3430 L/mol s (Table 10, run 2).
In agreement with the literature [19,35], the catalyst 2,4,6-Me3 LCrCl3/MAO/Al(i-Bu)3
produces PE with narrow MWD, proving that only one type of active center is formed in this
system. Lowering of the polymerization temperature results in a shift of the PE MWD curve
to the low-molecular weight region ( Fig.10, curve 1).
The increase in the PE MW at higher polymerization temperatures seems to be unusual,
because it is well known that the increase in polymerization temperature leads to the decrease
in molecular weight of polymers. To explain these contradictions the following considerations
can be suggested. Probably, in course of polymerization on the active centers of the catalyst
temporary interruption of polymer chain propagation reaction can occur (for example, due to
coordination of aluminium trialkyl on the active center) with formation of so-called
“dormant” centers. It is possible to assume that the time of “dormant” state of the active
centers decreases with the increase of polymerization temperature, resulting in formation of

polymer with the increased MW.
Table 10. The CP, kP and PE MWD data at ethylene polymerization with the catalyst
2,4,6-Me3LCrCl3/MAO/Al(i-Bu)3.
Run 1) τpol, T, Rb), CP, kР , Mw Mw/

0
min C Kg PE/ mol Cr mol/mol Cr L/mol s × 10-3 Mn
bar min
1 4 35 80 0.36 1410 0.8 1.3
2 3 70 260 0.76 3430 1.2 1.5
1)
Polymerization in heptane at ethylene pressure 3 bar, [Cr] =0.5-1×10-6 mol/l, Al(i-Bu)3/Cr =1000,
14
CO/Cr = 17-22; τCO = 5 min.
2)
2,0
1
1,5
2
d Wf / d log M
1,0
0,5
0,0
1 2 3 4 5
log M
Figure 10. MWD of PE produced over 2,4,6-Me3LCrCl3/MAO/Al(i-Bu)3 catalyst at different

polymerization conditions: (1) 350C, 4 min; (2) 700C, 3 min; (Number on the curve corresponds to the
number of experiment in Table 10).
Thus, the obtained data show that the active component of the catalysts based on 2,4,6-
Me3 LCrCl3 can be formed only in presence of MAO. The active centers of these systems
provide high PE yield in polymerization at 70 °C. Narrow MWD of PE samples obtained with
the systems (2,4,6-Me3LCrCl3/MAO) /Al(i-Bu)3, evidences that interaction of 2,4,6-
Me3LCrCl3 with MAO produce only one type of active centers and the catalysts of this type
can be regarded as single site catalysts. The number of active centers formed at the initial
moment of polymerization at 700C is high ( 0.76 mol/mol Cr), but these centers are very
unstable and are rapidly deactivated with polymerization duration. The catalysts (2,4,6-
Me3LCrCl3/MAO)/Al(i-Bu)3 are characterized by low reactivity at propagation reaction ( the
kP value is 1.4×103 L/mol s at 350C )
3. ETHYLENE-1-HEXENE COPOLYMERIZATION OVER THE

HOMOGENEOUS CATALYSTS BASED ON BIS(IMINO)PYRIDINE
COMPLEXES
An important property of polymerization catalysts is their ability to control the molecular
structure of the growing polymer by the copolymerization of ethylene with α-olefins. Data on
ethylene copolymerization with 1-hexene promoted by catalytic systems based on
bis(imino)pyridine complexes of Fe(II), V(III) and Cr(III) are presented in Table 11.
Table 11. Ethylene /1-hexene copolymerization with homogeneous catalysts based on

bis(imino)pyridine complexes
1) 2) r1
Catalyst T, [C6H12]/ Bu /
°C [C2H4] /1000 C
2,6-Me2LFeCl2/Al(i-Bu)3 35 3.2 < 1.0 >1000
Al/Fe=500
2,6-Et2LVCl2/MAO 60 3.2 4.8 200

MAO/V=500
2,4,6-Me3LCrCl2/MAO/Al(i-Bu)3 70 2.0 2.4 400

MAO/Cr=200
Al(i-Bu)3/Cr = 1000
3)
Me2Si(Ind)2ZrCl2+ MAO 60 25
1)
Co-monomers molar ratio in the polymerization medium
2)
Bu-branching content in the obtained polymer (13С NMR data)
3)
Data of ref. [55]
The copolymerization parameter r1 was determined using the simplified copolymerization

equation ([Cα]/[C2H4]pol = 1/r1[Cα]/[C2H4]react) where [Cα]/[C2H4]pol is the molar ratio between
the units of 1-hexene and ethylene in the copolymer, and [Cα]/[C2H4]react is the molar ratio
between the concentrations of the co-monomers in the reaction medium [54]. In comparison
with the well known catalyst based on zirconocene complex [50], the r1 values found for iron,
vanadium and chromium complexes were noticeably higher (Table 11). The obtained results
indicate that catalytic systems based on iron, vanadium and chromium bis(imino)pyridine
complexes display very low copolymerization ability.
CONCLUSION
The data presented above on the ethylene polymerization activities at different
temperatures for bis(imino)pyridine complexes with different transition metal center and the
Cp and kp values together with the data on Mw and MWD of the produced polymers are
summarized in Table 12.
Table 12. Comparison of bis(imino)pyridine complexes as homogeneous catalysts

for ethylene polymerization
T, Rp
Catalyst o Cp kp ×10-3 Mw· Mw/Mn
C kgPE/mol
mol/mol M L/mol·s × 10-3
M·min·bar
2,6-Me2LFeCl2 35 1700 → 0.41→0.039 49 → 15 44 → 115 4.6 → 12
(MSC) 100
2,6-Me2LCoCl2 35 130 → 80 0.23 → 0.14 3.6 1.8 1.8
(SSC)
2-t-BuLCoCl2 35 520 0.73 3.6 320 2.7
(SSC)
2,5-t-Bu2LCoCl2 35 100 0.48 2.4 1200 1) -
(SSC) 50 210 0.69 3.2 370 2.1
2,6-Et2LVCl3 35 90 0.18 2.6 5.7 2.5

(SSC → MSC) 60 870 → 0.50 → 0.31 16.5 → 6.3 5.5 → 11 2.2 →
210 4.1
2,4,6- 35 80 0.36 1.4 0.8 1.3
Me3LCrCl3 70 260 0.76 3.4 1.2 1.7
(SSC)
1)
Mv value (intrinsic viscosity data)
It is evident, that the catalytic behavior of bis(imino)pyridine complexes with close

composition of the bis(imino)pyridyl ligands essentially depends on the transition metal
center. The catalysts based on 2,6-Me2LFeCl2 are characterized by (1) very high activity at
low polymerization temperatures (35 °C) with different activators (both MAO and aluminium
trialkyls); (2) low thermal stability of the active sites; (3) formation of multiple active sites
and transformation of the active centers in the course of polymerization, (4) formation of
linear PE with high Mw and broad MWD; (5) the reduction of catalysts activity with
polymerization time is caused by decrease in the number of active centers and their reactivity
with polymerization duration.
Interaction of 2,6-Me2LCoCl2 with different activators produces only one type of active
site, characterized by (1) relatively low activity and low thermal stability; (2) PE with low
Mw and narrow MWD is produced with the catalysts based on 2,6-Me2LCoCl2; (3)
deactivation of the catalysts in course of polymerization is connected with the reduction of the
number of active centers, whereas their reactivity remains constant; (4) the molecular weight
of the produced PE is greatly affected by the size of the substituents at the o –positon in the
aryl ring of bis(imino)pyridyl ligand due to profound effect of these parameter on the transfer
reaction constant.
2,6-Et2LVCl3 is activated only upon interaction with MAO. Thus formed catalyst is
highly active within the broader temperature range (35-60 °C). At low polymerization
temperature (35 °C), it can be regarded as a single site catalyst producing PE with narrow
MWD. At higher polymerization temperatures (60 °C) the polymerization kinetics for this
catalyst becomes more complex: during the polymerization, the catalysts activity sharply
decreases, whereas Mw and Mw/Mn values of the produced PE increase. This catalyst acts as
a single site in the initial period of polymerization ( 5 min), producing PE with narrow MWD,
but with the increase of polymerization time the initial active centers are deactivated ( the Cp
value decreases) and new multiple active sites are formed in the system. The centers appear in
course of polymerization are less active than the initial ones and produce PE with higher MW.
As a result, the measured catalysts reactivity decreases whereas the Mw value of the produced
PE increases and MWD broadens.
Highly active catalysts based on 2,4,6-Me3LCrCl3 are formed upon interaction of
chromium complex with MAO at low MAO/Cr molar ratio. Only one type of active center is
formed in the systems (2,4,6-Me3LCrCl3/MAO/Al(i-Bu)3, producing PE with low Mw and
narrow MWD at polymerization temperatures at 35-700C.
Thus, bis(imino)pyridine complexes of Co(II), V(III) and Cr(III) generate single site
catalysts. However, in the catalysts based on RnLVCl3 in the course of polymerization
simultaneously with the deactivation of the initially formed highly active centers, new active
centers appear, resulting in broadening of MWD of the resulted PE.
The main difference between RnLFeCl2 catalysts and the catalysts based on RnLCoCl2 ,
RnLVCl3 and RnLCrCl3 is formation of multiple active centers upon interaction with
activators of different types: MAO or AlR3.
Iron and cobalt-based systems are inactive at the temperatures higher than 50 °C. The
active centers of the catalysts with RnLVCl3 and RnLCrCl3 as active component are
noticeably stable and these systems exhibit high initial activity at 60-70 °C. Comparison of
the catalytic properties of bis(imino)pyridine complexes with similar ligand framework has
shown that in polymerization runs at 35 °C the value of maximum activity decreases in the
order 2,6-Me2LFeCl2> 2,4,6-Me3LCrCl3> 2,6-Et2LVCl3> 2,6-Me2LCoCl2, whereas the values
of PE yield forms another order: 2,4,6-Me3LCrCl3 >2,6-Me2LFeCl2 >2,6-Et2LVCl3 ≈ 2,6-
Me2LCoCl2 because of different stabilities of these catalysts (Table 12). Activity of these
catalysts depends on both the number of active centers and the value of propagation rate
constants. Additionally, the yield of PE depends on the stability of these centers ( the decrease
in Cp values with polymerization time). The kp values are very high for the catalysts based on
the iron complexes ( 50-15×103 L/mol s, 350C) and rather low and similar for the complexes
of Co, V and Cr (3.6-1.4×103 L/mol s, 350C). The number of active centers depends on
polymerization conditions ( duration, temperature, activator) and varies within a broad range
(0.76 - 0.04 mol/mol M). The Mw values of PE are mainly determined by the substituents in
the aryl ring of bis(imino)pyridyl ligand, however the transition metal also affects the PE
molecular weight: the Mw values of PE produced at 35 °C decrease in the order 2,6-
Me2LFeCl2» 2,6-Et2LVCl3> 2,6-Me2LCoCl2 ≈2,4,6-Me3LCrCl3.
ACKNOWLEDGMENTS
The authors are grateful to Prof. K.P Bryliakov and Dr. I.E. Soshnikov for preparation of
iron, cobalt, vanadium and chromium bis(imino)pyridine complexes, used in our study.
The work was supported by the Russian Foundation for Basic Research (grant No. 07-03-
00311).
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Chapter 4
RATIONAL DESIGN OF CHIRAL RUTHENIUM

COMPLEXES FOR ASYMMETRIC HYDROGENATIONS
Jiří Václavík, Petr Kačer and Libor Červený*

Department of Organic Technology, Faculty of Chemical Technology
Institute of Chemical Technology Prague
Technicka 5, 166 28 Prague 6, Czech Republic
INTRODUCTION
Thorough optimization of reaction conditions for maximum yield is the essential
prerequisite of every reaction conducted on an industrial scale. In the field of asymmetric
chemistry, an additional yield requirement arises, i.e. the stereoselectivity of the reaction. The
plethora of fine chemical products available on the world market indirectly demands constant
improvements in the production processes and literally dictates an individual, made-to-
measure solution for the best efficacy. The relentless expansion of the product range thus
demands rapid but reliable tools for finding the optimal reaction conditions for a synthesis of
the chiral product in question.
Naturally, there is no catalyst to suit all substrates. Much like enzymes, almost every
reaction requires at least a slightly modified catalyst or reaction conditions. Trial-and-error
syntheses and subsequent testing of all (at first sight) potentially effective catalysts are as
costly and time consuming as traditional combinatory methods, due to immense possibilities
of the catalyst and substrate structures. Many of the complexes prepared by these laborious
procedures finally prove ineffective when trying to utilize them in a stereoselectively
catalyzed reaction. Therefore, the objective is to synthesize only those truly offering the
desired behaviour. While only a few metal centres can be used effectively (namely Ru, Rh,
Os, Ir), the auxiliary ligands offer infinite solutions of key changes to the structure. The
rational design has become a well-known term to describe the process of fine-tuning the
ligand. Although this chapter focuses on Ru catalysts, Rh complexes are also mentioned,
*
Corresponding author: Phone: +420 220 444 214, Fax: +420 220 444 340, E-mail: libor.cerveny@vscht.cz.
128 Jiří Václavík, Petr Kačer and Libor Červený
owing to the high parallelism of these two coordination centres in the field of asymmetric
hydrogenation.
The term “rational design” comprises the practice of altering the molecular structures
aided by computational modelling. Bearing in mind the structure of the chiral product, an
experienced theoretical-organic chemist should be able to assemble a well-founded series of
ligands offering good possibilities of achieving the desired performance in a particular
situation. This process involves a competent rejection of structures with a significant potential
of failure with regards to enantioselectivity. Given the vast number of possibilities, such a
process would ideally be performed automatically, i.e. either by high-throughput
experimentation (HTE) techniques, which have been amply reviewed [1] and are not covered
within this chapter despite their rapid development in recent years, or through computational
chemistry. This preliminary virtual assay is often referred to as in silico screening. Recently,
high-capacity virtual ligand libraries have been created and analyzed, allowing a systematic
description of existing ligands and a subsequent prediction of the properties of analogues.
Computational methods on various levels of complexity are available, enabling us to refine
the search results by stepwise reduction of the number of potentially successful catalysts by
employing more sophisticated techniques.
Nevertheless, it ought to be noted that empirical findings still maintain an inimitable and
supreme role. Molecular modelling is doubtless a powerful tool but one needs to appreciate
that even models of the highest accuracy are still an approximation and will never yield 100%
match.
Nowadays, there are thousands of ligands used in asymmetric syntheses and millions of
further possibilities. Nonetheless, the reader is advised to note that this chapter concentrates
on those used in asymmetric hydrogenation. Ligands used for asymmetric hydroformylation,
hydrocyanation, reductive amination, allylic alkylation, hydrosilylation etc., are not covered.
Occasionally, however, some of these are mentioned as explanatory references that may be
applied to all ligands, including those for hydrogenation.
HISTORICALLY IMPORTANT CHIRAL LIGANDS

Phosphorus – A Foundation Stone of Asymmetric Synthesis
The aim of this chapter is to outline the progression in asymmetric catalysis involving
phosphorus, as this ligand class undeniably belongs to the most important compounds used
for reduction of prochiral alkenes and ketones in particular. If it were not for the first
phosphorus-based ligands, the branch of asymmetric synthesis might not exist to the
contemporary extent at all. [2] The most important ligands, which formed the very foundation
depicting the development in this field within the past decade, are presented below.
The origins of successful chiral ligands date back to 1971 when Kagan and Dang
introduced the bisphosphine chelate DIOP 1 [3] possessing C2 scaffold chirality. Independent
of this work, Knowles et al. discovered the monophosphine CAMP ligand 2 [4] which
enabled a comfortable synthetic procedure of L-DOPA, the most extensively-used drug for
clinical treatment of Parkinson’s disease. Knowles, well aware of this ultimate discovery,
readily developed a structural analogue DIPAMP 3 [5] which was soon synthesised on an
Rational Design of Chiral Ruthenium Complexes … 129
industrial scale – the famous Monsanto L-DOPA synthesis. These two ligands prosper from
phosphorus atom chirality and surprisingly, since their introduction, not many monodentate
ligands had emerged by 2000. In 1977, Fryzuk and Bosnich prepared a very simple yet potent
C2-symmetric diphosphine CHIRAPHOS 4. [6] Incorporated in a Rh complex, CHIRAPHOS
proved very selective in α-N-acylaminoacrylic acids hydrogenation.
P
O PPh2 PPh2
OMe
P MeO
O PPh2 P
Me PPh2
(R,R)-DIOP 1
OMe (R,R)-CHIRAPHOS 4
CAMP 2 (R,R)-DIPAMP 3
Figure 1. The pioneering phosphorus chiral ligands.
In 1980, a huge step forward was made by Noyori et al., [7] who presented the axially
chiral BINAP ligand 5. This synthesis was successful only thanks to the persistence of the
Noyori group as their discovery was preceded a 4-year search for the best procedure. [8] The
introduction of this bisphosphine ligand (Figure 2) substantially extended the range of alkenes
possible to hydrogenate, namely the noteworthy syntheses of naproxen, [9] α-tocopherol,
morphine or dextromethorphan, all of these being widely-used pharmaceuticals. Additionally,
reduction of functionalized ketones afforded valuable products, in particular carbapenem [8]
and levofloxacin antibiotics, to name the most significant. Selective catalytic hydrogenation
of simple ketones, however, still remained unapproachable due to the lack of Ru-binding
heteroatoms in the substrate structure. This only became possible after the introduction of the
RuII XylBINAP-diamine and TolBINAP-diamine systems [10] (6 in Figure 2), the diamine
being DPEN or DAIPEN. The true rationale behind this advancement was a path-breaking
metal-ligand bifunctional mechanism [11] which did not require the substrate to bind to the
Ru centre directly, and could thereby proceed without the need for the substrate to contain
Ru-coordinating structures. For example, the new system allowed a convenient synthesis of a
potent antidepressant (R)-fluoxetine. [8] Interestingly, BINAP is able to operate both on RhI
and RuII coordination centres, yet with the opposite stereoselectivity owing to different
reaction pathways. [12]
In 1991, Burk [13] added BPE 7 and DuPhos 8 to the expanding ligand collection for
prochiral alkene reduction using Rh catalysts. These ligands (Figure 3), belonging to the
bis(phospholane) group, were the first representatives possessing the rigid phosphocyclic
structure which proved to be very powerful in terms of enantioselectivity of the complex. As
a result, many analogues emerged which are mentioned further in the text. The
ferrocenyldiphosphine JosiPhos 9 type of ligand, developed by Togni et al., [14]
demonstrated the possibility of applying various substitutions to the phosphorus atoms, thus
optimizing the structure of the ligand to serve a particular substrate.
Cl
P NH2
PPh2 Ru
PPh2 P NH2
Cl
Ru-diamine-diphosphine
(R)-BINAP 5
OMe
Cl H2 Cl H2
PAr2 N PAr2 N
Ru Ru OMe
PAr2 N PAr2 N
Cl H2 Cl H2
Ar = 3,5-Me2C6H3: Ar = 3,5-Me2C6H3:
6a [RuCl2{(R)-XylBINAP}{(R,R)-DPEN}] 6c [RuCl2{(R)-XylBINAP}{(R)-DAIPEN}]
Ar = 4-Me-C6H4: Ar = 4-Me-C6H4:
6b [RuCl2{(R)-TolBINAP}{(R,R)-DPEN}] 6d [RuCl2{(R)-TolBINAP}{(R)-DAIPEN}]
Figure 2. Noyori’s original BINAP ligand and Ru-BINAP/diamine complexes.
PR2
R R R R
Fe PPh2
P P P P
R R R R R = i-Bu, Ph, cyclohexyl
BPE 7 DuPhos 8 JosiPhos 9
Figure 3. Bis(phospholane) and ferrocenyldiphosphine ligands.
BINOL-derived monodentate ligands [15d] (Figure 4) bring a new approach, establishing

a whole new family of chiral auxiliaries whose chirality rests on the phosphorus atom rather
than the ligand backbone. Although Knowles’ CAMP has already been discussed as an
efficient monophosphine, the real boom in this area started as late as 2000! Soon after Kagan
highlighted the importance of research in this area, [16] pioneering structures emerged from
laboratories of Pringle, [15a] Reetz [15b] and Feringa, [15c] who introduced
monophosphonites, monophosphites and monophosphoramidites, respectively (10a,b,c).
Until then, it was believed that chelating ligands were needed to obtain asymmetric induction.
The advantages of Rh catalysts bearing monodentate ligands comprise mainly high
modularity and straightforward syntheses from cheap precursors. [17] This feature enabled de
Vries et al. [18] to implement a high-throughput experimental route for finding the right
catalyst. Morever, mixing these ligands together was a very interesting method yielding high
enantioselectivity, since they were monodentate and more of them coordinated to the central
atom at the same moment. Typically, so-called homocombinations occured when only one
ligand was used, however one-pot usage of two different ligands (not necessarily 1:1) led to
selectivity-enhancing heterocombinations. [19]
O O O R
P R P OR P N
O O O R'
monophosphonites 10a monophosphites 10b monophosphoramidites 10c
Figure 4. BINOL-derived monodentate phosphorus ligands.
Although many monodentate ligands were BINOL-based, some noteworthy alternatives

were available (Figure 5), as in the case of Me-SIPHOS 11 developed by Zhou [20] (2002),
which was a very powerful tool for α-aryl enamide asymmetric reduction. Additionally,
Helmchen [21] introduced in 2002 a bulky phosphane derivative 12 capable of highly
selective itaconates hydrogenation. The structure of diazaphospholidines 13 [22] manifested a
great deal of creativity; a recent derivative (discussed below) performed extremely well in an
acrylate reduction, regardless of the fact that this ligand was not originally intended for
hydrogenation reactions.
N O Ph
P
O N
O P OR
P
H N
MeSIPHOS 11 12 13
Figure 5. Non-BINOL monodentate phosphorus ligands.
Ligands Used in Asymmetric Transfer Hydrogenation
In 1995, Noyori et al. [23] disclosed the pilot catalytic system RuCl(η6-
arene)(arenesulfonyl-diamine) 14 which initiated the development of asymmetric transfer
hydrogenation (ATH) as a remarkable branch in chiral synthesis. Up to now, we have only
described catalysts used for standard asymmetric hydrogenation (AH) where gaseous H2 was
used as the reducing agent. ATH, utilizing organic compounds (IPA, HCOOH/TEA
azeotrope) as the source of hydrogen, was yet one step closer to enzymes which naturally
utilize designated hydrogenation media such as NAD(P)H or FADH2.
Ar 14
NHTs NH2
Ar: benzene,
p-cymene,
Cl Ru N SO2R mesitylene NH2
15
NHTs
H N R: tolyl,
Ph 1-naphthyl,
H 2,4,6-(CH3)3-C6H2
Ph NHTs NH2
NH2 NHTs
R2
16a:R1 = Me, = H
R2
R1 NH 16b: R1 = Me, R2 = Me
16c: R1 = Me, R2 = Bn 17a: R1 = Me, R2 = H
NH 17b: R1 = H, R2 = Me
16d: R1 = Me, R2 = CH2(C6H4)C6H5
OH 17c: R1 = Ph, R2 = H
16e: R1 = Ph, R2 = Bn 17d: R1 = H, R2 = Ph
R1 OH
R2
Figure 6. Ru half-sandwich complexes and examples of their auxiliary chiral ligands.
The original catalysts were primarily Ru or Rh half-sandwich species, employing an

aromatic ligand and a chelate auxiliary (Figure 6). In the case of Ru, the η6-arene is
represented by benzene or its derivatives. [24] The number of options started to grow
intensely with the evaluation of all utilizable chiral auxiliaries. Many of them have been
tested, i.e. from the original N-sulfonylated 1,2-diphenylethylenediamines [25] (included in
14) to various diaminoindanes 15, [26] β-amino alcohols 16 [27] or 2-azanorbornyl alcohols
17. [28] However, all of these performed well only in the ATH of aromatic ketones. An
example of an aliphatic ketone ATH is presented further in the text.
The authors were of the opinion it was beneficial to the readers to provide a concise
historical review of the evolution of ligands capable of asymmetric reactions catalysis. It
should by now be obvious that the pool of fundamental structures, serving nowadays as a
“brainstorm source”, is truly voluminous. Since the reader at this point should have at least a
basic knowledge of how such structures could be approached, the following text proceeds to
the chiral ligand rational design.
RATIONAL DESIGN OF CHIRAL LIGANDS

Since their discovery, aforementioned ligands have been modified extensively by means
of rational design. The systematic approach attempts to categorize (and individually quantify)
all possible changes that can be made to the original structures. Commonly adverted sites
have been the steric surroundings of the donor atoms (usually P, N, O), the backbone profile,
the angle formed by the donor atoms and the central atom etc. (see Figure 7). Although these
parameters influence one another to a certain extent, causing an obstacle to a systematic
assay, this approach has remained a popular and promising way for a ligand enhancement,
especially when followed by proper analytical methods. In the next section, relevant alterable
parameters are described and real examples provided.
Figure 7. The main features of a ligand: backbone, donor atoms (labelled D) and their substituents (R).
The ligand’s steric and electronic properties can be modified in several ways: 1) the
backbone, 2) substitutions at the ligating sites, 3) changes contributing to the firmness of the
scaffold, but not affecting the donor atoms’ positioning, and 4) major adjustments affecting
the angle between the ligand atoms and the metal. In the following section, this is discussed in
detail.
1) Substitutions on the Backbone
The main backbone framework can be extended in specific directions, thus shaping the
active site cavity for the substrate. Protruding substituents are able to retain the substrate
molecule in a specific position, favouring the transition state leading to the desired
enantiomer. The substitution may also evoke a transfer of electron density which is further
discussed in a separate section. Below, a few examples of backbone substitution are
presented.
A superb example of this is the improvement of BINAPO 18 by introducing ortho- aryl
substituents to produce o-BINAPO 19 [29] (see Figure 8). Molecular modelling revealed [30]
that most probably, the additional aromatic rings hindered the phenyl groups on phosphorus
atoms (in Figure 8 displayed with arrows), which made the ligand less flexible. BINAPO, a
rather ineffective ligand compared with others of its kin, was thus improved to the much more
effective o-BINAPO.
Monodentate ligands derived from a BINOL skelet (Figure 9) have also been subject to
research in this category. Interestingly, ortho- substitution has been examined in two different
versions. Reetz and co-workers introduced a number of different substituents into the position
3, but not to 3', changing its symmetry from C2 to C1 and adding a second stereogenic centre
onto the phosphorus atom. This way, novel diastereomeric ligands 20a,b,c were identified,
giving excellent ee values whether pure, or mixed diastereomerically. [31] By contrast, Zhang
[32] inserted phosphine substituents into both 3 and 3' positions, increasing the number of P
atoms in the molecule from one to three. It should be noted that these phosphine-
phosphoramidite ligands 21 are bidentate, with the third phosphorus atom left unbound.
R
Ph
O PPh2 O P Ph R = Me: Me-o-BINAPO
R = Ph: Ph-o-BINAPO
O PPh2 O P Ph R = 3,5-Me2C6H3: Xylyl-o-BINAPO
Ph
R
BINAPO 18 o-BINAPO 19
Figure 8. BINAPO and o-BINAPO.
OR OR
O Me O
P N P N
O Me O
R = Me, Bn, Bz R = Me, Bn, Bz

20a 20b
R PPh2
O Me O R
P N P N
O Me O R
R = Me, Ph, SPh, PPh2

R = Me, Et
20c SiMe3, Si(Ph)3 21
Figure 9. Ortho- substituted BINOL ligands.
2) Substitutions on the Donor Atoms
The steric effect of the donor atom substituents is basically similar to the backbone
substitution, i.e. to hold the substrate molecule in the optimal position enabling the desired
enantioface differentiation. However, the residues may be electron-donating or electron-
withdrawing, which naturally affects the electronic properties of the ligand; this is further
analysed in a separate section. Several examples are discussed below to point out the diversity
of donor atom substitutions.
Phosphorus monodentate ligands 10 can bear a variety of R- groups at the donor site.
Originally, these were relatively simple as Me, Et, i-Pr, Ph etc. Gradually, more special
alternatives have emerged (Figure 10). The laboratories of Chan et al. [33] came up with an
inventive idea introducing a ferrocenylphosphine group, thus giving birth to highly versatile
phosphine-phosphinites and phosphine-phosphoramidites 22. These ligands performed
outstandingly in reducing α-dehydroamino acid derivatives (ees up to >99). Moreover, 22a
exhibited the advantage of improved air and water stability over the original phosphinite
which allowed much a more comfortable usage. The introduction of the ferrocenylphosphine
group has also been studied by other research teams. [34]
A different approach was taken by Zheng et al. who successfully applied carbohydrate
substitution to the monophosphite backbone. [35] His D-Mannitol derivative ManniPhos 23,
benefiting from an inexpensive facile synthetic procedure, displayed excellent
enantioselectivity in reduction of various functionalized olefinic substrates. As these
examples represent only a fragment of possible substitutions, a curious reader may find more
in the relevant literature. [36]
Alongside the BINOL-based monodentate molecules, extremely stable
diazaphospholidines were reported by Gavrilov and co-workers. [37] From these multi-
purpose ligands, a noteworthy adamantane-1-ol derivative 24 proved to be a highly selective
ligand in methyl 2-acetamidoacrylate Rh-catalysed hydrogenation, demonstrating that
adamantane also possessed qualities of a valuable structural component in modular ligand
design.
Ph O
Me
O O
PPh2 OR
P X O
O Fe O O P
O
Ph O
22a X = -N(Me)- ManniPhos 23
22b X = O
Ph
N
P O
N
24
Figure 10. Innovative donor atom substitutions on monodentate phosphorus ligands.
3) Changes Towards Rigidity
BPE 7 and DuPhos 8 represent perfect examples of a backbone structural modification

leading to a similar, yet more sterically-constrained product. Comparing these two structures
(Figure 3), one would draw the conclusion that BPE is rather flexible within the ethylene
region, whereas aromatic DuPhos is built more rigidly. Although BPE shows excellent results
regarding selectivity, DuPhos performs even better on the same substrate series, [13] most
probably thanks to the enhanced rigidity of the backbone.
In general, structural rigidity has proven extremely good for stereoselectivity which led
Zhang et al. to the development of a phosphabicyclic ligand PennPhos 25, [38] capable of
highly selective reductions of simple ketones, cyclic enamides and enol acetates. Many other
ligands utilizing the phosphorus chirality together with phosphacyclic structural rigidity have
been introduced by this group (see Figure 11 for a few examples), [39] where BINAPINE 29
[40] belongs to the most remarkable ones.
HH
Me
HH
Me P P
P P
Me t-Bu P P
t-Bu
Me t-Bu t-Bu
(R,S,R,S)-Me-PennPhos 25 TangPhos 26 DuanPhos 27
Me Me P t-Bu
P P
N N Me P t-Bu
Me
Me Me
bis(azaphosphorinane) 28 BINAPINE 29
Figure 11.Zhang’s phosphocyclic ligands.
Regarding ATH ligands, their structure can be reinforced using an additional covalent
bonded bridge between the η6-aromate and sulfonyl group of the chiral ligand [41] (30a in
Figure 12), thus preventing the aromatic ring from its rotation. As a result, there is only one,
pocket-like ligand with a fairly fixed conformation. Moreover, the tether may also be directed
to the other end of the diamine. These so-called reverse-tethered catalysts (30b in Figure 12)
displayed a higher activity in comparison to the original non-tethered structures. [42] The last
example to be mentioned (30c [43]) harnesses an improved tether structure containing a
benzene ring. Furthermore, the ligand includes another six-membered ring connecting the
donor atoms, which in combination with the revamped tether enables superior structural
rigidity, affording distinct asymmetric induction. A wide palette of enantiopure substrates was
prepared using a Rh complex containing this ligand, where cyclohexylmethyl ketone (ee 87
%) was of a particular interest given the fact it was an aliphatic substrate.
SO2 Ts
Cl Ru N Cl Ru
N Rh
Ts
H N N
N N H
H H
Ph Ph
Ph Ph
30a 30b 30c
Figure 12. Tethered catalysts for ATH.
4) Major Changes to the Backbone
Changing the “length” or conformation of the backbone leads to a different positioning of

the donor atoms towards the metal centre, which most probably dramatically affects the
complex properties. There is no universal and exact way of measuring the steric qualities of a
ligand, however, a number of approximations exist that enjoy popularity. Naturally, each of
them has its own optimal area of usage based on the models they are based on. In the next
section, the most familiar ones are discussed in detail (i.e. the cone angle and the natural bite
angle) and other reported steric descriptors briefly described.
The Cone Angle

The cone angle (Figure 13a), mostly suitable for axially symmetric monodentate
phosphines, was first implemented by Tolman. [44] Its definition is based on a space-filling
model of a Ni-PR3 complex, where the Ni-P distance is fixed at 2.28 Å. In the case of general
unsymmetrical ligands PR1R2R3, three semicone angle values (θi/2) were separately
measured, averaged and doubled, which afforded the θ as well (Figure 13b). Ferguson et al.
[45] complemented the concept by introducing the so-called ligand profiles for bulky
phosphines, allowing another useful measure of the ligand shape all the way round. It needs
to be said that every coordination centre has its own typical M-P bond length meaning that the
application of the cone angle to complexes of other metals should be considered. However,
the cone angle is still being used very often for its simplicity, high reputation and good
agreement with factual data. Therefore it is not surprising that Tolman’s extensive review
[44] belongs to the most cited Chem. Rev. articles.
Figure 13. a,b) The cone angle θ; c) The bite angle βn; d) Comparison of θ and βn on a chelating
ligand.
There are two ways to obtain a cone angle value. From an X-ray analysis, [46] one can
deduct the value with reasonable accuracy, however, a solid crystalline sample is required.
Since the angles in a crystalline substance may (and usually do) differ from those in a
solution, which are the conditions where the ligands actually operate, a computational
approach is often preferred as a convenient method for finding conformations representing the
true energy minima, which are more likely to exist in a solution. An example of this can be
found in a recent paper by Gavrilov et al. [37]
The Bite Angle

The cone angle may be used for the evaluation of chelating ligands, [47] although a
different approach is preferred since the sterical description of phosphorus chelating ligands
by the cone angle is not often very conclusive. Bidentate ligands are seldom round shaped and
thus the cone angle is often not a precise measure. This is the reason why the natural bite
angle is preferred (βn in Figure 13b,c). Its definition is as follows: The natural bite angle is the
preferred chelation angle determined only by ligand backbone constraints and not by metal
valence angles. [48] Therefore, this concept does not depend on the selection of the transition
metal. An important feature is that adjusting the bite angle, one may observe significant
differences both in activity and selectivity of the catalyst. [49] It has become a very important
parameter of the backbone steric properties and several real applications are presented below
to highlight its significance.
TunePhos 32 [50] is a textbook example of adjusting the bite angle (and smart ligand
fixation as a bonus), as illustrated in Figure 14. Stemming from MeO-BIPHEP 31, Zhang
et al. appended an alkanediyl bridge to this structure (C1 to C6 long), discovering direct
correlation between the bridge length and the ligand natural bite angle. It has been
demonstrated that every substrate favours different bite angle range. [39] Another clear and
convenient way of ligand optimization was thus invented.
O
MeO PPh2 PPh2
( H 2C ) n
MeO PPh2 PPh2
O
(R)-MeO-BIPHEP 31 (R)-TunePhos 32
Figure 14. Original MeO-BIPHEP. TunePhos bite angle variability.
However, the aforementioned bonus in the form of the ligand fixation is necessary to
achieve the selectivity, as demonstrated in the following example. Figure 15 depicts
MiniPHOS 33, [51] Bis-P* 34 [52] and substituted 1,3-bis(phosphino)propane 35, the only
difference between each being the backbone length – the longer the chain, the more active the
catalyst obtained for dehydroamino acids reduction. Nevertheless, ligand 35 displayed very
poor selectivity (14 % ee) in contrast to 33 and 34 which both showed outstanding results
(99.0 and 99.9 % ee, respectively). [53] This was due to the four- or five- membered
constrained chelate cycles these ligands formed with the metal. The atropisomeric structure of
BINAP, BINAPO, TunePhos and others provided the necessary stabilization of the six-
membered ring formed upon complexation. Hence, the ligand backbone rigidity should not be
omitted when experimenting with the bite angle, although exceptions to this exist. [54]
t-Bu P P Me t-Bu P P Me t-Bu P P Me

Me t-Bu Me t-Bu Me t-Bu
(R,R)-MiniPhos 33 (S,S)-BisP* 34 35
Figure 15. MiniPHOS, Bis-P* and bis(phosphino)propane structures.
A major change to the backbone moiety, although not affecting the bite angle, could be
observed in the structure of a monodentate ligand 36 derived from H8-BINOL, as displayed in
Figure 16. The Rh-H8-MonoPhos catalyst offered excellent selectivity in asymmetric enamide
reduction, mostly 3% higher than in the case of original MonoPhos (i.e. 10c possessing the
NMe2 heelpiece). [55]
O R
R = R' = Me or Et
P N R = -CH(Me)Ph, R' = H or Me
O R' R + R' = -(CH2)4-
H8-BINOL 36
Figure 16. H8-BINOL ligands.
Other Steric Descriptors

In some cases, the above descriptors are less suitable for characterizing the ligand steric
requirements. For this reason, further descriptors are provided in the following text,
regardless of their special burden related to their empiric dependency. One theoretical
approach, in particular the MESPsteric parameter, is mentioned further in the text, i.e. at the
end of the electronic parameters subsection, as the method is mainly oriented towards the
electronic properties and this steric parameter followed as a consequence.
Koide et al. defined the pocket angle [56] for chelating phosphorus ligands as an
alternative to the cone angle used preferentially for monodentate ligands. This method
similarly utilizes CPK models obtained from crystallographic data. Perpendicular (θ||) and
parallel (θ⊥) pocket angles were established so as to completely describe the non-conical
bidentate ligand.
White and co-workers introduced an interesting solid angle (Ω) concept [57] which is
based on projecting the ligand atoms on the inside of a unit sphere as depicted in Figure 17.
The metal is considered a light source and the solid angle is then calculated from the shadow
area cast upon the sphere. In addition to the aforementioned ligand profile, White
simultaneously proposed a radial profile [57b] as a plot of dependence of Ω on the P-M
distance. Radial profiles comparison has enabled further analysis of the ligand steric
requirements. A recent paper by Guzei [57c] represents a good complement to this topic with
some improvements included.
1440 Jiří Václavík, Petrr Kačer and Libor
L Červený
Fiigure 17. The liigand projectionn used for solid angle (Ω) calcuulation.
Recently quite
q popular, the S4' steric parameter waas first introdduced by Orpeen [58] and
ussed as a descrriptor by Cunddari et al. [59] For the modeel complex M-PXn, S4' can be worked
ouut easily as a difference bettween ∑(<M-P-X) and ∑(< <X-P-X). Therrefore, the S4'' parameter
caan be obtainedd directly from
m crystallograpphic data using only the corrresponding boond angles,
w
which makes it very user-frriendly. Underrstandably, coomputational attempts
a havee also been
reeported on booth full DFT T and ONIOM M [60] – deesignated DFT T-S4' and ONNIOM-S4',
acccordingly (coomputational methods
m are diiscussed furthher in general)..
Fiigure 18. Harveey’s He8_ring (aa) and He8_weddge (b). The parrentheses repressent a general sppacer or the
prresence of two monodentate
m liggands.
Figure 18 displays
d an altternative to thee cone angle established
e by Harvey and co-workers.
c
They introduceed the He8_steeric parameterr [61] which simulatess spaccial interactionns between
thhe monodentaate ligand in question
q and other
o ligands in cis configuuration in an octahedral
coomplex. Also known as the He8_ring, a planar p He8 cyccle of a constraained radius (2.5
( Å) was
pllaced oppositee the phosphoorus atom at a fixed distancce of 2.28 Å and the wholle structure
opptimised, startting with a pree-optimised frree ligand geoometry. The innteraction energy (which
iss in fact repressented by the He
H 8_steric desscriptor) between the ligandd and the He8 auxiliary
a is
allmost exclusiv vely of a steriic origin as thhe He-P distannce (3.383 Å) exceeds the sum s of van
deer Waals radiii of the two atooms (3.2 Å), which
w is the reeason why eleectronic contributions are
almost negligible. A similar concept, called He8_wedge, has been soon afterwards developed
for P,N bidentate ligands. [62] In this situation, it turned out to be more convenient to fix four
He atoms (strictly speaking, every second atom of the eight-membered ring) in the ligating
sites of an octahedral complex in a fixed 2.28Å distance from the transition metal. The angles
between He atoms were constrained at 90°/180° values and the starting ligand geometry was
adapted from a tetrahedral zinc complex. After setting the donor-metal distances P-M, N-M
(2.28 and 2.00 Å where possible, or the shortest possible distances for ligands where this
could not be accomplished), the metal was deleted and the resulting structure optimized. The
practical usage of these parameters is further discussed in this text.
Computational Methods
Before the electronic descriptors are presented, a general outline of computational

approaches is provided. Theoretical chemistry offers a variety of tools that may be utilized to
obtain the descriptor values and thus molecular modelling of such systems can be carried out
using molecular mechanics, semi-empirical or DFT levels of theory. Pure ab initio computing
comes into question merely in the case of the simplest phosphines due to its enormous
hardware requirements and employing DFT counts with reasonably small molecules and a
well selected basis set. [63] Consequently, one probably chooses the level of theory according
to their computational resources, the system investigated and the accuracy aspired.
Nowadays, most of the ligands can be computed on the semi-empirical or even DFT level,
owing to technological advances in computing centres. However, large biomolecules,
representing another quickly evolving field of rational design, still have to settle for molecular
mechanics or molecular dynamics. [64] An illustrative comparison of QM (MINDO/3,
MNDO) and MM (MM2) was presented by Chin et al., [65] however these model phosphines
were not actually real ligands used in asymmetric synthesis.
Electronic Ligand Descriptors
Having described the steric parameters of ligands, it is necessary to give an account of

descriptors concerning their electronic properties. Since these can actually be applied to all
structural changes, it has been described at the end of this subsection, while the account of the
sterical descriptors was given more conveniently together with the backbone adjustments.
Parallel to steric descriptors, there are several pioneering concepts among the electronic ones,
followed by certain advanced successors. In a chronological sequence, the descriptors based
on experimental work are first demonstrated, while the section is concluded with an overview
of computationally accessible parameters.
In his landmark work, [44] Tolman investigated a large series of PR3 ligands incorporated
in a [Ni(CO)3PR3] model complex and ranked them according to νCO(A1) in CH2Cl2 solution,
defining the Tolman’s electronic parameter (TEP) scale. A direct correlation was shown
between the stretching frequency νCO(A1) and electronic properties of the phosphine ligand.
Electron-donating R groups increase the phosphine basicity, causing electronic enrichment of
the metal and subsequent transfer of electron density into the CO sσ* antibonding orbital.
Naturally, this weakens the CO bond and its stretching frequency decreases. On the TEP
scale, the most basic phosphine P(t-Bu)3 was selected as a reference ligand in the Ni complex
(with the A1 band of 2056.1 cm-1) and other phosphines were related to [Ni(CO)3P(t-Bu)3]
through the parameter χ.
Crabtree [66] generalized this approach and showed that, as a matter of fact, any
carbonyl-containing complex may be used in the TEP scale. Tolman’s system was
insufficient for complexes with two cis-configured phosphine ligands/a chelating ligand, so
Crabtree employed a cis-[Mo(CO)4L-L] complex to measure νCO(A1) and designed a formula
which enabled a conversion of these values onto the original Ni-complex based TEP scale.
Therefore, every complex may possess its own ν scale, which can be chosen according to the
ligand requirements, however an interconversion is possible between these scales. [67]
The Lever electronic parameter (LEP) [68] is a useful alternative to those experimentally
obtained by IR spectroscopy. Considering Mn/Mn–1 redox potentials to be fully additive,
Lever defined the LEP parameter as 1/6 of ERu(III)/Ru(II) potential for RuL6 in acetonitrile.
Similarly to TEP, his extensive list of LEP values for over 200 ligands has also been used as a
benchmark for validating theoretical methods. [73,74]
Among alternative experimental ways of investigating the phosphine basicity is the usage
of 13C NMR spectroscopy. Chemical shifts of carbons from CO ligands in various complexes
were found to be affected by the presence of other donor ligands. Taking advantage of those
central atoms which are also NMR active nuclei, coupling constants (1JPB, 1JPSe, 1JPPt, 1JPW)
were studied as well. While these coupling constants were found to be related to the
corresponding bond strength (and to P basicity, accordingly), the 1JPC constants did not seem
to be linked to the phosphorus basicity at all. [67] Regarding the basicity, one would have
obviously expected some kind of experimental pKa or pKb studies. Indeed, pKa values of
conjugated acids to a series of PR3 tertiary substituted phosphines were measured e.g. by
Allman and Goel, showing a fine correlation with the electronic data. [69]
However, these experimental models exhibited one or more major drawbacks which
provoked others to come up with improved solutions. Firstly, electronic properties of the
ligand were our target, while these methods afforded only indirect results via a certain
complex. Secondly, the overall electronic effects of the ligand (described by Tolman’s
electronic parameters) were a sum of two opposite phenomena – the σ-donation of the
phosphorus lone pair into the metal’s vacant orbitals, and the π-backdonation from the metal
to an empty orbital of the phosphorus atom (arguably σ* [70]). Considerable efforts have
been made to isolate these two factors, revealing the complexity of this problem. Giering and
co-workers proposed an appreciable concept, [71] where the phosphines were distributed into
three classes: σ-donor/π-donor, σ-donor and σ-donor/π-acceptor according to correlation of
EL°' of Mn and Fe complexes with pKa values of the phosphines in question. Afterwards, they
came up with a sophisticated quantitative analysis of ligand effects (QALE), [72] stepwise
establishing three parameters describing the electronic properties of phosphines. These
parameters were χd (representing σ donor ability), πp (characterizing π acidity) and Ear, whose
notation stemmed from its original purpose of an aryl effect description, although its role is
now considered operative even in non-aryl substituted phosphines.
The next focus is on theoretical investigative methods which are invaluable in the field of
ligand design due to the experimental unavailability of required data and an appealing
possibility to predict ligand properties. As an analogue to TEP, Crabtree reported the
computed electronic parameter (CEP) [73] using frequency calculations on a DFT level of
theory. Since DFT frequency jobs investigating bulkier phosphines tended to be
computationally very demanding, Cundari and co-workers [74] devised a semi-empirical

quantum mechanical approach allowing a wide range of feasible calculations. Having had a
good agreement with TEP, LEP and CEP, their semi-empirical parameter SEP turned out to
be a highly suitable computational option for quick in silico testing.
Having followed these simple analogues to the original works of Tolman, more advanced
methods were developed. The findings of Suresh and Koga, [75] who have established the
convenient molecular electrostatic potential (MESP), i.e. a computational method consistently
describing electronic properties of substituted phosphines (PR3), presented a handy example
relevant to this topic. The MESP approach did not require any experimental background and
therefore could also be used to predict the properties of new structures in silico. It was the
bare ligands that were evaluated, eliminating any influences of a complex species. The key
idea was finding the global minimum Vmin of MESP pertaining to the lone pair region of the
phosphine ligand, which was exactly the area of interest as the lone pair electron density was
connected to the phosphine basicity. Similarly to Tolman’s ranking, P(t-Bu)3 showed the
highest “σ-donating power” by having the lowest Vmin value. PH3 was included as well to set
up a reference point of unsubstituted phosphine; if electron donating groups were present,
Vmin value decreased and vice versa. Moreover, the results fairly correlated with Tolman’s
νCO(A1) scale, pKa of PR3 conjugate acids, ∆E of a complex formation reaction and finally
∆H° and E° for an iron complex redox reaction (FeII/FeI).
In 2006, a noticeable attempt was made by Suresh [76] to separate electronic and steric
properties, again using the MESP computational concept. ONIOM method was used to
achieve this: the surroundings of phosphorus atom (in each case bearing the hydrogen atoms,
i.e. PH3) were calculated using a DFT level of theory, while the R groups were treated with
molecular mechanics. In this configuration, the positioning of the link hydrogen atoms of PH3
depended on the steric requirements of the neighbouring R groups. This “tampering” with the
phosphine bond angles affected the p-character of the lone pair, enabling the steric effect of
the phosphine substitution to be observed.
Evidently, the number of ligand steric and electronic descriptors is significant and only a
limited selection is presented here. For this reason, the interested reader is encouraged to
study cited literature for more ligand descriptors. [77]
Reaction Mechanism Analysis
This chapter would not be complete without an account of the mechanistic aspects of
asymmetric catalysis. Profuse works have been dedicated to this field in order to understand
the reaction mechanisms, yielding an invaluable expertise in the form of highly detailed
information on the very nature of the catalytic process. In the following text, the
computational analyses of the transition states (TSs) are described, and a rationale of the
origin of enantioselectivity is included, albeit in a very brief form. DFT analysis of transition
states (TS) is discussed as well as some computationally cheaper approaches which may
partially or completely avoid costly QM calculations. The investigation of the full catalytic
cycles is not covered within this text given the complexity of the problem.
Describing the relative positioning of the molecules (i.e. substrate and catalyst) during
TSs explains its relation to the reaction’s enantioselectivity. When a prochiral substrate is
present in the chiral environment of the catalyst, certain options for its approach to the
complex are more sterically and electrostatically [78] favoured than others. Every route is
then followed by a more or less probable diastereomeric TS. The successful ligands used in
AH and ATH are chiral rigid molecules which strive for the reaction to proceed preferentially
via the favourable TSs leading to the desired enantiomer. The energy difference between the
favourable and disfavourable TSs determines the reaction ee and is temperature dependent.
[79] In other words, raising the temperature leads to a stereoselectivity decrease.
The quadrant approach has been the most utilized one for TSs analyses. The space
surrounding the catalyst is divided into four equal quadrants and the entire problem is thus
more systematic. Some catalysts, like 14, are designed advantageously to fully occupy three
quadrants, so as to disallow formation of TSs within these regions. In such a case, TSs may
be explored computationally in detail thanks to their limited number. However, others are
much more complicated, like e.g. BINAP with 68 possible TSs. [80] As the quadrant
approach has already been well described, relevant literature is cited. [53,81]
If only a few TSs are likely to form for structural reasons, thorough computational
analysis on a DFT level is feasible on contemporary resources, as long as the molecules are
not too big. Although such a quantum-mechanical approach yields very precise outcomes
with respect to geometries, better methods, like MP2, should be used for energy calculations.
Despite the extreme usefulness of such accurate results, these can really be obtained by
investigating a rather small catalytic system. For larger molecules, alternative procedures
need to be employed.
The QM/MM method is the most popular way of reducing the computational resource
needs, [82] dividing the entire system into sub-areas treated by different tools. The active
catalytic site is thus modelled by QM methods due to higher accuracy requirements,
especially regarding electronic properties, while the surroundings are treated by MM, which
afford results good enough since these parts of the system are mostly sterically governed and
their description by a force field is sufficient.
Another possibility, developed by Norrby, [83] allows TSs analyses merely on a MM
level. This method is called QM-guided MM (Q2MM) and employs custom force fields
derived from previous QM calculations. An important feature of Q2MM is that these
modified force fields actually allow the TSs to be calculated as energy minima, which can be
accomplished with ordinary MM methods.
The process of the substrate approaching the catalyst can be modelled as well, [84]
revealing the differences between the four quadrants. Such an analysis may provide us with
useful reasoning as to why the reaction does not take place through a TS within a certain
quadrant, while in others it proceeds with high activity and/or selectivity.
CONTEMPORARY TRENDS IN CATALYST DESIGN

In an ideal world, it would be possible to predict catalyst properties for a certain
stereoselective reaction entirely in silico. Even though the reality is still far from this
prospect, promising attempts have recently been emerging, proposing sagacious routes for
ligand computational screening by employing state-of-the-art research technology. Although
these “prototypes” have not yet been implemented into a routine use, they will certainly
facilitate the development of subtle techniques useful in ligand design.
A successful solution requires solid foundations applicable to a broad variety of

situations. Obviously, this is mostly conditional on a proper application of the knowledge
obtained by investigating the ligand steric and electronic descriptors, which has already been
outlined. Already the fact that such a large-scale ligand screening combines several
techniques of limited accuracy (i.e. choice of descriptors, the computational level of theory)
implies that the entire process is rather delicate and every component should be well-
considered to reach the required robustness.
The idea of a ligand map has been brought into play, showing that within a certain region
of the map, functionally similar ligands should reside. This was already broached by Tolman
[44] who plotted νCO vs. θ and showed characteristic areas of differently substituted ligands
(e.g. P(OR)3 and aliphatic PR3 only occurred in certain areas, each of their own). Then he
added a third parameter (generally denoted Z), which would depend both on θ and νCO, and
obtained a 3D landscape revealing the ratio of θ and νCO effect on Z in a slope-shaped
manner. This way, Tolman was e.g. able to elegantly demonstrate that 13C NMR chemical
shifts were mainly related to the electronic properties, whereas ΔH for reactions of excess
phosphorus ligands with a certain Pt complex proved to be sterically-governed. Although
Tolman used corporeal models to manually 3D-plot his results, he showed an invaluable way
of ligand mapping. Consequently, with a reliable set of descriptors and solid framework, more
precise ligand space reference points could be established. Here, we give an account of the
most recent attempts.
Cundari and co-workers [59] developed Tolman’s primary ideas and presented
stereoelectronic phosphine maps based on MM/semi-empirical calculations. Their conclusion
was that alkyl and aryl phosphines were surprisingly similar in terms of both steric and
electronic properties. They identified a gap in the map pertaining to the phosphines with very
low basicity, as in the case of e.g. P(t-C4F9)3, and pointed out the unusual qualities of cyclic
phosphines which expanded the map to a considerable extent.
Ligand Knowledge Base
In 2006, the group of Professor Harvey [61] came up with a set of computational
descriptors of monodentate phosphorus ligands which they called the ligand knowledge base
(LKB). The target of this project has been an automated global ligand descriptor assemblage,
capable of interpreting experimental data and, more importantly, predicting the properties of
unknown species. An emphasis was put on careful selection of enough reliable descriptors
and proper statistical evaluation methods in order to create a consistent infobase applicable to
a variety of molecules. In other words, some descriptors needed to be excluded due to their
excessive specificity, low sensitivity or difficult in silico automatization, but at the same time
a sufficient number of them had to be utilized to record all important features of the ligands.
Since experimental parameters were not uniformly accessible, Harvey’s group chose to
exploit crystallographic databases by means of molecular modelling on DFT level of theory,
using both supercomputers and distributed computing Grid methods. A series of 61
representative ligands was used, with the aim of including a wide range of compounds,
including symmetric (PA3), asymmetric (PA2B) and several utterly exotic molecules. Given
the availability of a wide range of empirical data for monodentate phosphines, a comparison
of these with theoretical descriptors was made possible, showing the feasibility of the whole
concept. Some utilized descriptors were also contextualized with similar but more often used
ones to justify their applicability (for example, He8_steric was contextualized with Tolman’s
θ, which actually was not used for LKB at all). The ligands were also investigated in both free
and in protonated and borane adduct forms. Their Pd complexes were also utilized to obtain
information on their electronic properties. In the end, the following decriptors were used:
HOMO and LUMO energies, proton affinities, adduct binding energies, NBO charges,
geometry descriptors indicating the differences after complexation, and several steric
parameters (He8_steric and S4' [58]).
As the number of often substantially correlated descriptors was quite high, the so-called
principle components (PCs) were derived from the descriptors as their linear combinations.
Chemically similar ligands tended to cluster in certain regions of the PC1 vs. PC2 plots,
which represented a next step after Tolman’s pioneering ligand map. Although the
quantitative interpretation of these maps did not prove reliable owing to PCA sensitivity to
outlier values, the qualitative information obtained by this method became quite useful.
Multiple linear regression (MLR) was also utilized to confirm the correlation between empiric
data and calculated descriptors, thus enabling prediction of experimental parameters for
unknown ligands investigated computationally. Later, Harvey et al. reported a similar concept
applicable for chelating P,P- and P,N- ligands, which they called LKB-PP. [62] They used a
similar selection of descriptors but applied some bidentate-related ones as the ligand bite
angle or He8_wedge. This way, the first chelating ligand map was proposed. In comparison to
the original monophosphine configuration, the usage of linear regression for predictive
purposes turned out to be limited due to scarcity of appropriate experimental data.
Three Spaces
Inspired by quantitative structure-activity and structure-property techniques (QSAR,

QSPR) commonly used for drug discovery in the pharmaceutical industry, Rothenberg et al.
[85,86] showed that in silico screening of even highly extensive libraries could be
accomplished without any MM or QM calculations or three-dimensional models. Of course,
the simplification in the form of 2D topological descriptors did not offer very accurate results
but was sufficient enough for a preliminary exploration of large ligand sets (i.e., over 105). As
they pointed out, [86] even the MM level 3D calculations handled only around 100 ligands
per hour, while 2D descriptors were able to analyze ca. 100,000 species per hour. This way,
potentially useful areas of the ligand space could be quickly discovered and further explored
by more accurate methods to actually identify (or predict) the most satisfactory molecules.
Nevertheless, their most significant contribution was the development of a complex
system for the construction and refinement of virtual catalyst libraries. [87,88] They specified
their search to an organometallic catalyst utilising bidentate ligand, which was disassembled
to the very basic building units. Consecutively, three multi-dimensional spaces A, B, C were
established. Discrete space A comprised all catalyst structures to be explored; each point in
the space uniquely determined a different structure; while each dimension in A pertained to a
different building block (ligating, backbone and residue blocks). Space A was inherently
connected to continuous space B, composed of catalyst descriptors and reaction conditions.
Finally, continuous space C was defined to comprise figures of merit (TOF, TON, ee, etc.),
enabling efficient catalysts identification. Spaces B and C shared a connection through
QSAR/QSPR modelling methods and this way, one could observe the desired properties (C)
related to the actual catalyst structures (A).
This idea represents a major step forward since it has contrived to link the real catalyst
performance properties to its structure. Developing and improving such a model is both
intriguing and desirable as it can be a very powerful means of catalyst rational design,
especially if accompanied by real laboratory experiments.
Simulated Evolution
Very recently, Riant et al. [89] opened another innovative way of computational
searching for the best catalysts using simulated evolution. At first, a library of Noyori-type
ATH catalysts was assembled and evaluated by means of HTE. Subsequently, a mother
generation G0 was brought together from this library either manually or randomly, and
utilizing a custom-programmed genetic algorithm, some of the best catalysts were reached
evolutionarily, even when using only 10 % of the library for G0 creation. Obviously, the goal
of this method is to find the majority of good catalysts in a few generations. If developed
further, the simulated evolution might be another promising way of chiral catalyst design.
Nonetheless, one should be vigilant in using these methods because, as was succinctly
pinpointed by Rothenberg: “Just because a program did not crash does not mean that the
results are meaningful”. [90] Correct statistical data interpretation and thorough validation of
the computing models are vital for the models to be both employable and trusted.
CONCLUSION
This chapter has attempted to present a concise insight into the contemporary methods of
catalyst design applicable not only to Ru complexes used in asymmetric hydrogenation but
also to various other catalytic systems. In order to be able to effectively master the extensive
catalyst/ligand libraries and discover new species by reliable predictive models, a robust set
of yardsticks is critical to properly describe the ligands and complexes. These descriptors
were presented and discussed in terms of their efficacy, reliability and applicability for in
silico compound searching. Nevertheless, a cursory computational search may often prove
insufficient and fallible, calling for more sophisticated methods as full scale QM calculations
or reaction mechanisms analyses. Regardless of the vast availability of the tools exploiting
theoretical chemistry, the genuine in silico catalyst design still remains a great challenge.
Although computational methods afford an enormous assistance, practical experiments still
play the decisive role.
Due to an immensely rapid development in this exciting field, only the basic idea of the
whole process could be presented, citing the relevant literature for further details. The toolbox
for asymmetric synthesis has developed extremely within the past four decades and is still a
key area of contemporary research in this field.
ACKNOWLEDGMENT
The authors wish to acknowledge with gratitude the financial support by the Grant
Agency of the Czech Republic (Grant GACR 104/09/1497) and the Ministry of Education of
the Czech Republic (Grant CEZ: MSM 604 613 7301).
LIST OF ABBREVIATIONS
AH: asymmetric hydrogenation
ATH: asymmetric transfer hydrogenation
BINAP: 2,2'-bis(diphenylphosphino)-1,1’-binaphthyl
BINAPINE: 4,4'-di(t-butyl)-4,4',5,5'-tetrahydro-3,3'-bi-3H-dinaphtho[2,1-c:1',2'-
e]phosphepin
BINOL: 1,1'-bi-2-naphthol
BIPHEP: 2,2'-bis(phosphino)-6,6'-dimethoxy-1,1'-biphenyl
BisP*: (S,S)-1,2-bis(alkyl-methylphosphino) ethanes
BPE: 1,2-bis(phospholano)ethane
CAMP: o-anisylcyclohexylmethylphosphane
CEP: computed electronic parameter
CHIRAPHOS: bis(diphenylphosphino)butane
CPK: Corey-Pauling-Koltun
DAIPEN: 1,1-di(4-anisyl)-2-isopropylethylenediamine
DFT: density functional theory
DIOP: 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane
DIPAMP: 1,2-bis[(o-anisyl)-(phenyl)phosphino]ethane
DPEN: 1,2-diphenylethylenediamine
DuanPhos: 2,2'-di(t-butyl)-2,3,2',3'-tetrahydro-1H,1'H-(1,1')biisophosphindolyl
DuPHOS: 1,2-bis(phospholano)benzene
ee: enantiomeric excess
H8-BINOL: 5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyl-2,2'-diol
HOMO: highest occupied molecular orbital
HTE: high-throughput experimentation
IPA: isopropyl alcohol
JosiPhos: (R)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine
L-DOPA: levodopa; L-3,4-dihydroxyphenylalanine
LEP: Lever electronic parameter
LKB: ligand knowledge base
LUMO: lowest unoccupied molecular orbital
ManniPhos: monophosphites derived from D-Mannitol
Me-SIPHOS: N-Dimethyl-[1,1'-spirobiindane-7,7'-diyl]phosphoramidite
MESP: molecular electrostatic potential
MINDO: modified intermediate neglect of differential overlap
MiniPhos: (R,R)-1,1-bis (alkylmethylphosphino) methanes
MLR: multiple linear regression
MM: molecular mechanics
MNDO: modified neglect of differential overlap

MP2: Møller–Plesset perturbation theory of the second order
NBO: natural bond orbital
NMR: nuclear magnetic resonance spectroscopy
ONIOM: our own n-layered integrated molecular orbital and molecular mechanics
PC: principal component
PCA: principal component analysis
PCR: principal component regression
PennPhos: endo-2,5-dialkyl-7-phosphabicyclo[2.2.1]heptanes
QALE: quantitative analysis of ligand effects
Q2MM: QM-guided molecular mechanics
QM: quantum mechanics
QSAR: quantitative structure-activity relationship
QSPR: quantitative structure-property relationship
SEP: semi-empirical electronic parameter
TangPhos: 1,1'-di(t-butyl)-(2,2')-diphospholane
TEA: triethylamine
TEP: Tolman electronic parameter
TOF: turnover frequency
TolBINAP: 2,2'-bis(di-p-tolylphosphino)-1,1'-binaphthyl
TON: turnover number TS: transition state
XylBINAP: 2,2'-bis[di(3,5-xylyl)phosphino]-1,1'-binaphthyl
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Chapter 5
SUPRAMOLECULAR GEL CATALYST: BRIDGING

HOMOGENEOUS AND HETEROGENEOUS CATALYSIS
Jianyong Zhanga and Stuart L. Jamesb

a) School of Chemistry and Chemical Engineering, Sun Yat-Sen University,
Guangzhou 510275, China.
b) Centre for the Theory and Application of Catalysis (CenTACat),
School of Chemistry and Chemical Engineering, Queen's University Belfast,
David Keir Building, Stranmillis Road, Belfast, Northern Ireland BT9 5AG, UK.
ABSTRACT
Supramolecular gels have received growing attention in recent years. They represent
a novel type of soft materials which may find application in various aspects. Various
organogels and metallogels offer rich possibilities for catalysis. Supramolecular gels can
be used in catalysis by incorporating a catalytically active unit as part of the gelator.
There are three strategies in literature: 1) catalysis by discrete gelators; 2) catalysis by
coordination polymer gelators; 3) catalysis by post-modified gels. Unique new catalytic
properties can arise from combining gels with catalytically active centres. Interestingly
supramolecular gels show enhanced activity compared with their homogeneous
analogues in a number of cases. They exhibit some combined advantages of
homogeneous and heterogeneous catalysis.
INTRODUCTION
Precisely what is, and what is not, a gel has proved notoriously difficult to define [1-5].
Many, but not all, consist of two continuous phases which interpenetrate on the macroscopic
scale [1-10]. All of the examples discussed herein consist mainly of a liquid (e.g. water,
ethanol, hydrocarbon etc.) which interpenetrates with a persistent network structure, formed
by a second species, the gelator. Although such gels are mainly liquid (often > 97%), they
exhibit some rheological properties like those of a solid, for example they are elastic, meaning
that after deformation, up to a certain limit, the original shape is recovered [1-2]. The
156 Jianyong Zhang and Stuart L. James
apparent contradiction between their mainly liquid constitution, but solid-like rheology, is due
to the persistent character of the network, and its attraction to the liquid, which prevents the
liquid constituent from flowing freely (although the molecules of the liquid continue to
diffuse throughout the structure).
The network structures are often made up of fibres. These propagate and interconnect, or
entangle, within the liquid phase. Many supramolecular gels form reversibly. For example,
heating can cause a change to a simple liquid phase (sol) and subsequent recooling can reform
the gel. The temperature at which the transition occurs is the gel point (Tgel). Various
classifications of gels are commonly used. Gels formed by changing the temperature are
called thermotropic. Those formed by changing the concentration of the gelator are called
lyotropic. When the connections within the network are strong (e.g. predominantly covalent
bonds, or due to strong entanglement), this can lead to so-called strong gels.
Characteristically, such gels exhibit sharp, well defined gel points. Where network
connections are weak, or due to easily disrupted entanglement, this can lead to weak gels.
These typically do not have sharp gel points [3-5]. Both strong and weak gels can be
reversible. Gels with networks which are maintained by covalent bonds, and which are not
reversible, are often termed chemical gels. Gels which have networks maintained by weaker
intermolecular forces (and are normally reversible) are termed physical gels [9]. Distinction is
also often drawn between gels based on aqueous phases (hydrogels) [10] and those based on
organic phases (organogels) [7, 8].
The gelators themselves may be polymers, or inorganic particles [1-2]. Alternatively,
small molecules can also gelate by aggregating into fibres within the liquid phase [3-10]. This
type of supramolecular self-assembly can occur through solvophobic effects, hydrogen
bonding, metal coordination, van der Waals attraction etc. Alongside the general development
of supramolecular chemistry, the study of such small molecule gelators (often called low
molecular weight gelators, or LMWGs) has increased greatly in recent years.
Like protein, a gel has a primary (angstrom to nanometer scale), secondary (nano- to
micrometer scale), and tertiary structure (micro- to millimeter scale) (Figure 1). The primary
molecular level recognition promotes the aggregation of the gelator molecules, the
aggregation forms the secondary structure, such as fibres, micelles, sheets, vesicles and so on,
and finally the secondary aggregates are entangled to form the 3D tertiary structure to trap
solvent [10]. Hydrogen bonding is believed to be a common driving force for aggregation of
gelators in organic solvents via forming 1D hydrogen-bonded network, while in protonic
environments, solvophobic effects are more important to protect from solvent. However,
metal coordination is expected to play a key role in metal-containing gels. Metal coordination
may be employed to form 3D matrix when a metal complex is a gelator, and normally does
not disrupt the gel network when a gelator gelates metal-containing liquid. Other metal-
related interactions like metallophilic attraction are also important for the primary aggregation
in gels.
It is still difficult to predict whether a gel phase will form from knowledge of the
molecular structures of a liquid and a potential gelator. The molecular organization within the
fibres of a gel may be crystalline, and, for example, give rise to X-ray diffraction patterns
[11]. The difficulty in predicting gelation is therefore related to the difficulty in predicting
crystal structures, which is considerably complicated by polymorphism or supramolecular
isomerisation and relies on understanding the selection of a given supramolecular molecular
packing mode [12]. However, gels are potentially more complex to understand since they are
Supramolecular Gel Catalyst 157
often based on two components and the interaction between the liquid and the gelator also
needs to be understood. A gel may be thought of in some ways as a failed crystal, because
propagation has occurred predominantly in only one direction (if it is based on fibres) and
prevented in the remaining two. Due to the difficulty in predicting gel phases, many gels are
still discovered serendipitously. However, as will be seen below, certain families of gelator
molecules have emerged, and to a degree, their structural features (e.g. urea-type groups etc.)
may be incorporated into the ‘design’ of new gelators with a degree of optimism and
rationality. In this regard, it is also worth mentioning that Shinkai proposed that 1D growth of
the fibres may be correlated with the molecular packing [13,14], and Dastidar has proved this
point and show crystal engineering concept can be exploited to design simple LMWGs [15-
17].
Figure 1. The primary, secondary, and tertiary structure of a self-assembled supramolecular gel of a
urea-based LMWG [10].
Supramolecular gels have been found applications in various areas due to its unique two-
phase structure, nonometer-size matrix, and metal centre for metal-containing gels. They have
been applied in the food, cosmetic and petroleum industries, and potential applications as
stimuli responsive materials [18-20], template of various metal, inorganic and organic
materials [21,22], biomaterials [23] and electronic devices [23] have also been reported. The
fact that many supramelecular gels form reversibly makes them of interest as responsive
materials [18,24] (e.g. changing their physical state in response to physical or chemical
triggers) and the presence of metal ions enriches the scope for responsiveness itself (e.g. to
species which ligate or interfere with ligation [25], or by redox triggers [26]) and for signaling
that response (e.g. through a change in spectroscopic, electronic or magnetic properties
[27,28]). One of the interesting aspects of gels is their ability to template other structures,
especially porous materials. This is achieved by polymerization, precipitation or reduction of
precursors in the liquid phase, and subsequent dissolution or calcination to remove the gelator
network. The method offers extensive possibilities for controlling the morphologies of diverse
materials.
CHARACTERISATION TECHNIQUES
Various techniques can be used to gain structural information on different length scales
[10]. With regard to the molecular packing within the gelator, infra-red [29,30] and NMR
[31] spectroscopies can give information on the presence of hydrogen bonds, and more
generally the local environments [32] and motions [33] of functional groups. Absorption and
emission spectroscopies can give information on the packing (e.g. stacking) of aromatic
groups, for example [34]. Information on molecular packing modes can also be obtained from
analysis of wide X-ray diffraction combined with modelling [35]. In addition, comparison of
the X-ray powder diffraction patterns given by a gelator in its crystalline form(s) with that
from its gel can help to identify the gel’s molecular packing [11,36]. Small angle X-ray or
neutron scattering can give information on the packing, for example, of molecular stacks
within the fibres [37]. To investigate the larger scale structure, electron microscopy can be
applied. Due to the need for a high vacuum, sample preparation can involve preliminary
drying, but this can also cause to structural changes. Alternatively, cryoscopic-TEM and –
SEM can be applied in which the sample is prepared by rapidly freezing it to liquid nitrogen
temperatures to preserve the original structure and imaging performed at low temperature.
Rheological study [38–40] of gels can give information on the number and strength of
connections in the network. The temperature at which gelation occurs for thermotropic gels,
Tgel, may be measured by the so-called dropping ball technique. A small ball bearing is placed
on the gel, which is then heated until, at Tgel, the ball falls through the material. Spectroscopic
indications of Tgel may differ from rheological determinations since the former detects
association at the molecular level whereas the latter may depend on larger scale association.
By placing the gel between two surfaces, and inducing oscillatory shear in the gel by
movement of one surface, various parameters can be obtained including the complex modulus
(G*), the storage or elastic modulus (G') and the loss modulus or (G''). G' is a measure of how
much energy is stored in a material upon deformation, whereas G'' is a measure of the energy
lost as heat. Generally for strong gels, which are formed from strong network connections,
G'>>G''.
GEL FOR CATALYSIS

Traditional homogeneous catalysts have identical catalytic sites and clear structure-
activity relations, and usually provide high reaction rate and afford high selectivity and yield.
However, homogeneous catalysts have a number of drawbacks. For example, the problem of
recycling of the catalyst leads to loss of expensive catalysts and to impurities in the products.
To address the problems, heterogenising homogeneous catalysts by immobilisation is a trend
toward developing efficient catalyst recycling systems. Various structures including silicas,
zeolites and organic polymers have been developed for this purpose [41-43]. However, these
methods often suffer from difficulties to retain or raise the activity and selectivity.
Supramolecular gels have recently been used in catalysis as a new strategy to design
catalyst recycling systems. Supramolecular gels are characteristic of finite short ranged order
with periodically disordered arrangement of the building units, which are different with either
amorphous polymers or crystals with infinite long ranged order with periodic arrangement of
asymmetric units. The gel network has a large surface area in contact with solution.
Catalytically active motifs have been incorporated in supramolecular gels because of their
following advantages as catalyst [44]:
• Efficient and readily accessible. The gel has large specific surface area and the
catalytically active units located in the gel fibres are accessible to solute molecules.
Additionally the 3D porous structure of gels facilitates high molecular diffusivities,
and favours transport of large molecules to and from the active sites.
• Easy-to-handle. Embedding the catalyst into a 3D gel network allows for its easy
recovery after the reaction comparing with traditional homogeneous catalysts. The
solid-like properties of gels would result in facile isolation of the catalyst by simple
filtration.
• Well-defined objects (fibres) in the nanoscale. In contrast to conventional polymer-
supported heterogeneous catalysts, the structure of the catalytic sites in
supramolecular gels can be controlled at a molecular level. The gels contain well-
ordered arrays of catalytic or binding units or stimuli responsive subunits, because
supramolecular gels are formed from the ordered aggregation of small molecules
through non-covalent bonds to yield elongated supramolecules that further aggregate
to fibres.
• Dynamic supramolecular interactions may offer supramolecular gels some new
properties different from those of traditional supported catalysts. Because of the
reversibility of supramolecular interactions, supramolecular gelation can be easily
modulated by external stimuli, such as temperature, pH, light and other chemical or
physical stimuli, resulting in their potential applications in photonic, stimuli
responsive, sensing, or catalytic materials, drug release, etc.. Therefore, Catalytic
function of gels can be expected to be controlled by stimuli such as temperature,
concentration, pH.
• Rapid progress of supramolecular gels provides a rich pool for active catalysts and
allow for rational design and synthesis.
In general supramoelcular gel materials combine some advantages of homogeneous and

heterogeneous catalysis, as well as the special features of their supramolecular nature. In
addition, supramolecular gels may provide a suitable model for understanding of emergence
of life and construction of cell mimetics [45].
Catalytically active centres can be incorporated into gelators directly according to their
driving forces for molecular aggregation or by post-modification. Three strategies have
appeared in literature: 1) gelation by discrete organo-/metallogelators; 2) gelation by
coordination polymer gelators; 3) post-modification of a preformed gel with catalytically
active centre (Figure 2) [44,45].
Cat.
Cat.
Cat. L
Cat. L
Cat.
Cat. Cat.
L Cat.
Cat. Cat.
Cat.
a b c
Figure 2. Incorporation of catalytically active centre into gel networks (schematic representation): a)
gelation by discrete gelators; b) gelation by coordination polymer gelators; c) post-modification of a
preformed gel with catalytically active centre.
1. CATALYSIS BY DISCRETE GELATORS

1.1 Discrete Organogelator
Supramolecular organogels based on low-molecular weight gelators are formed through

reversible non-covalent interactions. The gels from LMWGs are typically formed by
dissolution of gelator in an appropriate hot solvent and subsequent cooling to a lower
temperature. They can be readily transformed into fluids by heating and are generally
thermoreversible. The dynamic nature of the system is also revealed by Escuder and Miravet
that a fraction of the molecules remain in solution in equilibrium with the phase separated
fibrillar material [46].
A report by Inoue et al. is among the earliest reports of organogel catalysis [47]. Using a
cyclic dipeptide cyclo-(S)-Phe-(S)-His (1) as catalyst, addition of hydrogen cyanide to
aldehydes were carried out as a gel at low temperature (-20 oC) when the solvent is toluene
(Table 1). Interestingly the gelation of the reaction mixture makes the degree of asymmetric
induction significantly increased. At -20 oC an extremely high enantioselectivity was
observed for the conversion of benzaldehyde to (R)-2-hydroxyl-2-phenylacetonitrile (97%
conversion with 97% ee). Following this observation, Danda found that high
enantioselectivity and high conversion was obtained in the hydrocyanation of 3-phenoxy-
benzaldehyde to (S)-2-hydroxy-2-(3-phenoxyphenyl)acetonitrile (92% and 91% ee) catalysed
by the cyclo-(R)-Phe-(R)-His (2) toluene gel [48]. The gelator can be recycled by extraction.
The reaction mixture is thixotropic, which has an important influence on the
enantioselectivity. As the viscosity of the reaction mixture is lowered, the enantioselectivity is
raised, whereas the conversion was not influenced (Table 2).
In these early reports, the self-assembled fibrillar structure of gels was poorly understood
and the gels were considered to be completely amorphous. In an subsequent effort for enzyme
mimicking, Guler and Stupp synthesised peptide amphiphile 3, which forms hydrogels at
concentrations greater than 0.1 wt% and pH above 6.5, arising from self-assemble of piptide
amphiphiles into nanofibres [49]. TEM revealed formation of high-aspect-ratio cylindrical
nanostructures with diameters of 7 ± 1 nm. In comparison, compounds 4–6 are soluble in
water to form polydisperse spherical aggregates with diameters ca. 15-20 nm (Figure 3). The
supramolecular aggregates were subjected to hydrolysis of 2,4-dinitrophenyl acetate, a model
ester compound, to 2,4-dinitrophenol at 25 oC and pH 7.4. Significantly higher catalyst
activity and stability was detected for the hydrogel of 3 than the others (Figure 4). The
activity enhancement is due to higher density presentation of reactive sites with significant
internal order on nanofibres relative to catalysts in solution and in spherical micelles.
Table 1. Asymmetric addition of hydrogen cyanide to aldehydes catalysed by the cyclo-

(S)-Phe-(S)-His (1) gel.
O
N
HN
NH NH
O
O 1 (2 mol %) HO CN
R H H
HCN (2 equiv), Toluene, -20 oC R
Entry Aldehyde Time/h Conv./% ee/%

1 benzaldehyde 8 97 97
2 benzaldehyde(p-OMe) 10 57 78
3 benzaldehyde(m-OMe) 8 83 97
4 benzaldehyde(o-OMe) 10 45 84
5 benzaldehyde(m-OPh) 8 97 92
6 benzaldehyde(p-Me) 10 78 96
7 benzaldehyde(p-NO2) 2.5 99 53
8 benzaldehyde(m-NO2) 8 100 4
9 benzaldehyde(p-CN) 8 100 32
10 2-napthaldehyde 1.5 61 91
11 6-methoxy-2-napthaldehyde 6 88 73
12 fufural 8 60 42
13 nicotin-3-aldehyde 0.5 73 54
14 cyclohexanecarbaldehyde 2.5 96 58
15 isovaleraldehyde 5 44 18
16 hexanal 8 90 56
17 pivalaldehyde 5 60 58
Table 2. Influence of thixotropy in asymmetric addition of hydrogen cyanide to 3-

phenoxy-benzaldehydes catalysed by the cyclo-(R)-Phe-(R)-His (2) gel.
O
N
HN
NH NH NC OH
CHO
O 2 (2 mol %) H
O O
HCN (2 equiv), Toluene, 6 h, 5 oC
Entry Rate of stirring/rpm Yield/% ee/%

1 150 97 74
2 200 97 86
3 250 97 92
4 300 97 92
N
HN R
O O O O N
H H H H H
N N N N NH2
N H 2N N N N N
HN H H H H
O O O O O
H
N
H2N 3, R = Palmitoyl
O 5, R = H
N
HN R
O O O N
H H
N N N NH2
N H2N N N N
HN H H O
O O O
H
N
H2N 4, R = Palmitoyl
O 6, R = H
Figure 3. TEM images of 3 (A), 4 (B), 5 (C) and 6 (D) [49].

Supramolecular Gel Caatalyst 163
Fiigure 4. Observved rate increasee in hydrolysis of

o 2,4-dinitrophhenyl acetate (H
His-Omet = L-histidine
m
methyl ester) [49
9].
O O
H H
N N
N 6 N
N
NH H H
O O HN
N
O O
O O H H
H H N N
N N N 6 N
N n N N
NH H H
H H O O HN
N
NH O O HN
7a-c, n = 1, 4, 6 O O
H H
N N
N 6 N
N
NH H H
O O HN
N
Fiigure 5. L-proline derivatives 7a-c,

7 multiple H-bonding
H interactions betweenn 7c, and SEM images of
thhe xerogels of 7c from MeNO2 and EtNO2 [500].
Miravet annd Escuder et al.

a recently repported that a series
s of L-prooline derivativves 7a-c are
caapable of selff-assembly intto organogelss in MeCN, ethyl
e acetate or
o toluene [500]. 7c also
foorms gels in MeNO
M 2 and EtNO2. SEM im mages of the xerogels revealed a fibrillaar structure,
w
which are microcrystalline as demonsttrated by X--ray powder diffraction (Figure ( 5).
Formation of aggregates through multiple H-bonding interactions is responsible for the gel
formation. An acid-base indicator dye, bromothymol blue, is drawn to its blue form in the
presence of the gel but remains yellow in the presence of a solution (Figure 6). Considerable
basicity enhancement of L-proline secondary amine is due to proximity of L-proline groups in
the gel fibres as compared to solution.
Figure 6. Evolution of bromothymol blue color during gelation of compound 7c in MeCN. The starting
yellow (not basic) solution turned into a blue (basic) gel [50].
Such a basicity enhancement leads to remarkably different catalytic activity towards the
aldol reaction between acetone and 4-nitrobenzaldehyde. Reactions were performed in the gel
phase, by diffusion of the aldehyde through a MeCN gel containing acetone. In solution, 7a-c
behave as enantioselective catalysts for the aldol reaction, whereas in the gel state, the
catalytic activity of the L-proline moiety in enamine-based aldol reactions is inhibited, and
they are basic catalysts inactive in the aldol reaction but active in the based-catalysed aldol
racemisation (Table 3).
Table 3. Results of racemisation of 4-hydroxy-4-(p-nitrophenyl)-2-butanone.
OH O
CHO O Cat., MeCN
+
O2 N 2 weeks, -20 oC O 2N
Entry Catalyst [catalyst] [catalyst] gel/mM Enantiomeric ratio (S:R)

sol/mM
1 7a-sol 6.5 - 1:4.0
2 7a-gel 6.5 5.5 1:2.9
3 7b-sol 2.4 - 1:4.0
4 7b-gel 2.4 9.6 1:1.3
5 7c-sol 2.4 - 1:4.0
6 7c-gel 2.4 9.6 1:1.2
Table 4. The Henry reaction of nitroalkanes and aldehydes catalysed by the 7c gel.
NO2 NO2 NO2 NO2

CHO HO
R R R R
Cat. (10 mol %)
+ R NO2
MeCN, 2 d + +
X
X X X
I II III
Entry R Reagent T/oC Yield of Yield of

nitroaldol/% II + III /%
1 Me 4-nitrobenzaldehyde 5 (gel) 99 -
2 Me 4-nitrobenzaldehyde 25 (solution) 15 5
3 H 4-nitrobenzaldehyde 5 (gel) 38 2
4 H 4-nitrobenzaldehyde 50 (solution) 46 33
5 H 4-chlorobenzaldehyde 5 (gel) 11 4
6 H 4-chlorobenzaldehyde 50 (solution) - 99
7 H 4-methoxybenzaldehyde 5 (gel) - -
8 H 4-methoxybenzaldehyde 50 (solution) - 100
The gel phase of 7c as active phase has been shown in the Henry nitroaldol reaction
between nitroalkane and aldehyde [51]. For catalytic studies, a solution of 4-
nitrobenzaldehyde was left to diffuse into the gel prepared in the corresponding nitroalkane.
A sharp change in catalytic activity was observed (Figure 8). Highly efficient catalytic
activity for the Henry reaction was only observed in the aggregated state upon gel formation
(Table 4). For example, a quantitative conversion of the aldehyde to nitroaldol was obtained
in the reaction of nitroethane and 4-nitrobenzaldehyde. The results suggest that the catalytic
activity of 7c can be regulated by minor temperature changes (5 and 25 oC) due to reversible
sol-gel transition. The reactions also work for highly and moderately reactive aldehydes (e.g.
4-nitrobenzaldehyde and 4-chlorobenzaldehyde). Different reaction mechanisms have been
proposed for the catalytic performance (Scheme 1). The reactions in the gel phase start with
the deprotonation of the nitroalkane by the secondary amine of L-proline through an ionic
pair type mechanism, while in solution formation of iminium intermediates may result in the
nitroalkene byproducts.
Miravet and Escuder et al. further designed an amphiphilic hydrogelator derived from L-
proline, 8 [52]. SEM revealed a network of ribbons of less than 300 nm in width and several
μm in length (Figure 8). X-ray powder diffraction of the xerogel confirmed a lamellar
structure bilayer with intercalation of the alkyl tails. For catalysis for the direct aldol reaction
between cyclohexanone and 4-nitrobenzaldehyde, reagents were topped on the gel dissolving
in toluene and the product was obtained with quantitative yield after 24 h at 5 oC with high
stereoselectivity (anti: syn 92:8, 88% ee). It is a heterogeneous catalytic system and after
decantation of the toluene phase the catalytic hydrogel could be reused for at least three times
with similar efficiency and stereoselectivity (Table 5).
Figure 7. Temperature controlled catalysis in the Henry nitroaldol reaction [51].
Scheme 1. Reaction mechanism of the Henry nitroaldol reaction [51].

O
H
N
N
H
NH O 8
Figure 8. Photographic and SEM images of the hydrogel of 8 [52].
Table 5. Direct aldol reaction catalysed by hydrogel-8.
O
O OH
CHO Hydrogel-8 (0.2 equip)
+
O2N Toluene-water
20 equip 1 equip NO2
Entry Ru T/o t/h Yield/% anti:syn ee/%

n C
1 25 16 >99 91:9 18
st
2 1 5 24 98 92:8 88
nd
3 2 5 24 >99 93:7 87
rd
4 3 5 24 >99 92:8 90
Dötz et al. reported that pyridine-bridged bisbenzimidazolium salts with long alkyl chains
1a-d efficiently gelate a variety of alcohols, MeCN, and other polar solvents [53]. TEM
revealed morphologies of 250-500 nm wide and several micrometer long straight fibres,
indicating a parrallel columnar packing (Figure 9). X-ray analysis, SAXS and 1H NMR
studies show that supramolecular interactions including π stacking between the aromatic
rings, H-bonding, and van der Waals interactions between the alkyl chains are responsible for
the gelation. The MeCN gels are efficient phase transfer catalysts with stirring for N-
alkylation of benzimidazole, benzotriazole and imidazole (Table 6). The catalysts can be
recovered after filtration and reused after regelation with MeCN.
N N N 9a, R = n-C16H33, X = Br
9b, R = n-C16H33, X = I
+ +
X- 9c, R = n-C12H25, X = I
N X- N
9d, R = n-C8H17, X = I
R R
Figure 9. TEM images of the gels of 9a-d formed from i-BuOH [53].
Table 6. Phase-transfer N-alkylation of benzimidazole, benzotriazole and imidazole

catalysed by gel-9.
cat. (5 wt%), 25% NaOH

X + ArH
X
MeCN, RT
Br Br Ar Ar
Entry X Ar Catalyst Time/h Yield/%

1 N benzimidazole gel 9b/MeCN 3 89
2 N benzimidazole gel 9a/MeCN 5 92
3 N benzotriazole gel 9b/MeCN 3 59
4 N imidazole gel 9a/MeCN 6 67
5 N imidazole gel 9b/MeCN 5 63
6 CH benzimidazole gel 9b/MeCN 3 90
1.2 Discrete Metallogelator
Discrete metal complexes have been recently reported to act as gelators [54,55]. Discrete
metallogelators self-assemble through multiple noncovalent bonds, such as H-bonding, π-π
stacking, solvophobic effects, electrostatic interactions and other supramolecular weak
interactions. The metal-ligand interaction is only a secondary force to form 3D gel matrix in
some sense, which can be understood to mainly form discrete complexes. Such gels involving
weak interactions may be transformed to a fluid by external stimuli (heating, sonication etc.)
to break these interactions and thus thermally reversible like their organogelator analogues.
Dötz et al. reported that a palladium CNC pincer Pd(II) carbene complex bearing long
alkyl substituents, 10, is a good gelator for normal organic solvents [56]. TEM revealed that
larger fibres are present in xerogels from protic solvents (e.g. MeOH, AcOH), while dense
networks of smaller fibres result from nonprotic solvent (e.g. DMF, DMSO, DMA, and THF)
(Figure 10). Thermoreversible sol-gel transition was observed for the gels at 50–60 oC. The
planarity of the metal-chelating pincer ligand may allow for aggregation by intermolecular π-
π interaction, enhanced by Pd···Pd interactions and van der Waals interactions between the
alkyl chains. Promising catalytic activity of the palladium pincer carbene gel was observed in
the double Michael addition of α-cyanoacetate to methyl vinyl ketone with in situ prepared
DMF and DMSO gels as catalyst under slow stirring (Table 7).
N N N
I-
N Pd N
n-C16H33 n-C16H33
I
10
Figure 10. TEM images of gels formed from palladium(II) pincer complex 10 [56].
Table 7. Double Michael addition of -cyanoacetate catalysed by gel-10.
i
Pr2NEt, cat.
+ NC CO2Et
O CH2Cl2, RT
NC CO2Et
Entry Catalyst k/[10-6 s-1] t1/2/h

1 10-gel/DMSO (4 wt%) 24.1 7.9
2 10-gel/DMF (4 wt%) 10.4 18.5
3 10 5.5 35
4 blank 3.8 51
You et al. examined the morphology evolution of a series of supramolecular aggregates

based on dinuclear metallocyclic Pd2L2 units formed by semirigid imidazole derivatives 11a-f
and Pd(OAc)2 (Scheme 2) [57]. Ligands 11a and 11b are soluble in DMSO and assemble into
spherical particles with the average diameters of ca. 46 and 66 nm, respectively, revealed by
dynamic light scattering DLS, AFM and TEM studies. Whereas ligands 11c-f bearing
phenolic hydroxyl groups with Pd(OAc)2 at a 1:1 molar ratio form gels in DMSO, DMA, and
other DMSO solvent mixtures. H-bonding among the phenolic hydroxyl groups, the anions,
and the solvent molecules plays an important role in the gelation process. 3D globular
networks, formed by interconnection of smaller spherical aggregates, lead to gelation as
revealed by TEM (Figure 13). The gels formed by 11c-f and Pd was used to catalyse the
phenylation of indole with phenylboronic acid. The 11c-Pd(II) gel afforded the product in
about 50% yield, higher than those of the soluble complex and the xerogel (less than 5%
yield).
N N
N N
11a: R1 = Me, R2 = H; OH
R1 R2
11b: R1 = H, R2 = H;
OH
11c: R1 = Cl, R2 = OH;
N 11d: R1 = Me, R2 = OH; N
N N
11e: R1 = t-Bu, R2 = OH; 11f
11c-Pd(II) gel, O2 (1 atm)

H + PhB(OH)2 Ph
N AcOH, RT, 10 h N
H H
Scheme 2. Phenylation of indole with phenylboronic acid catalysed by 11-Pd(II) gel.

Figure 13. TEM and AFM height images of spherical aggregates of 14a-Pd (a,b,c) and 14b-Pd (d,e,f),
and TEM image of the 14e-Pd xerogel obtained from DMSO [57].
2. CATALYSIS BY COORDINATION POLYMER GELATORS

Gels formed by coordination polymers, infinitely extending metal-ligand assemblies with
bridging organic ligands, are of interest considering a large number of metal ions and organic
ligands available [54,55]. Metal-ligand interactions are the main driving force to form the 3D
gel network as coordination polymers act as gelators. Such coordination polymer gels based
on metal-ligand interactions generally can not be redissolved upon heating and do not show
thermoreversible gel-sol transitions.
Xu et al. reported a type of polypyridine-based palladium(II) coordination polymer gels
[58]. Reactions of polypridine ligands 12a and 12b with Pd(OAc)2, 12c with Pd(OAc)2 or
[Pd(en)(H2O)2](NO3)2 in DMSO gave metallogels after 4 h ~ 2 months which did not flow on
inversion of the vial. In the oxidation of benzyl alcohol to benzaldehyde on exposure to air,
the wet gel prepared from ligand 12a exhibited the optimal result, giving a total catalytic
turnover (72) about twice that of Pd(OAc)2, and three that of the corresponding precipitate
from acetone (Scheme 3).
N
OH OHOH OH N N
NH N
N NH HN
HN N
N N
N N HN
N N N
N N N
12a 12b 12c
12-Pd(II) gel (0.1 mol %) CHO

OH
air, 90 oC, 2 h
Scheme 3. Aerobic oxidation of benzyl alcohol catalysed by the 12-Pd(II) gels.
A larger tripyridine ligand 13 was later reported by our group to form coordination
polymer gels with Pd(COD)(NO3)2 in a range of mixed organic solvents (e.g. MeOH-CHCl3)
[59]. The gels can be formed with a range of Pd/13 ratios from 1:1 to 1:4 during a shorter
period of 2 min to 2 h. 1H NMR, FT-IR, and fluorescence spectroscopic studies showed a
combination of Pd-N coordination, H-bonding, π-π stacking being present in the gel
aggregates. SEM revealed an interesting morphology evolution of spherical assemblies to
fibrous structures in the xerogels with decreasing Pd/13 ratios from 1:1 to 1:4 (Figure 11).
The 13-Pd(II) gel/xerogels efficiently catalyse the Suzuki-Miyaura coupling under
atmospheric conditions (Table 8, entries 1–4). Interestingly, the fibrous network has been
shown to have higher activity than spheres in Suzuki-Miyaura coupling. The xerogel catalyst
can be recovered by simple filtration for at least 5 times and reused without significant loss of
activity.
N
HN O
2+
1/4 equiv Pd 1 equiv Pd2+
N N
N H N
O N
NH O
N 13
Figure 11. Morphology evolution of Pd-pyridyl gels depending on Pd/L ratio.
The gel nanofibres based on the Pd-13 gel can be supported on superparamagnetic
magnetite (Fe3O4) nanoparticles by simply mixing 13, and Pd2+ in CHCl3-MeOH with a Pd/13
molar ratio of 1:1 in the presence of magnetite nanoparticles [60]. The presence of magnetite
nanoparticles was unambiguously confirmed by TEM and magnetism studies (Figure 12).
The superparamagnetic 13-Pd(II)-MNPs xerogel show similar activity in Suzuki-Miyaura C-

C coupling reactions (Table 8, entries 5–8). The xerogel can be magnetically isolated with a
permanent magnet and reused for 5 times in the reaction of iodobenzene and phenylboronic
acid.
Table 8. Suzuki cross-coupling of aryl halides and phenylboronic acid catalysed by the
13-Pd(II) (1:1) gel and the 13-Pd(II)-MNPs xerogel.
13-Pd(II) gel (1 mol %)

R X + B(OH)2 R
3 equip Na2CO3,
X = I, Br 1.5 equip MeOH, 60 oC
Entry X R Catalyst Time/h Yield/%

1 I H 13-Pd(II) gel 90 >99
2 Br H 13-Pd(II) gel 15 28
3 Br COMe 13-Pd(II) gel 15 >99
4 Br OMe 13-Pd(II) gel 15 26
5 I H 13-Pd(II)-MNPs xerogel 120 >99
6 Br H 13-Pd(II)-MNPs xerogel 60 78
7 Br COMe 13-Pd(II)-MNPs xerogel 15 97
8 Br OMe 13-Pd(II)-MNPs xerogel 30 27
Magnetic gel
N
HN O
mixed
+ Pd2+ + Fe3O4
N N
N H N product
O N
NH O substrate
13
N
a b
Figure 12 (Continued).
c d
Figure 12. Magnetic gel nanofibres for organic transformation, and TEM images of the 13–Pd(II)
xerogels before (a,b) and after (c,d) loading of magnetite nanoparticles [60].
Uozumi et al. reported a palladium-based coordination polymer gel based on a tripodal

flexible triphosphine 14 [61]. A yellow gel is obtained upon reaction of 14 with
PdCl2(NCPh)2 in toluene at 100 oC for 24 hours. 31P MAS NMR of the gel showing a singlet
at 20.0 ppm is consistent with complexation of palladium species and the ligands through Pd-
P coordination bonding. The xerogel is insoluble in water and several types of organic
solvents (chlorinated solvents, toluene, methanol). The xerogel’s catalytic ability was
investigated in the Suzuki-Miyaura coupling of aryl halides with boronic acids in water. High
yields of coupling products were obtained and Electron-deficient as well as electron-rich aryl
iodides/bromides readily coupled with arylboron reagents bearing para-, meta-, and ortho-
EWG and EDG substituents to give the corresponding biaryls in 80-99% yields. The catalyst
could be recycled at least four times with retention of similar activity as demonstrated in the
reaction of iodobenzene with 4-tolylboronic acid (Scheme 4).
PPh2
O 6
O
O O
6 PPh2
O
6
O
Ph2P 14
14-Pd(II) xerogel
(0.05 mol %)
I + (HO)2B
3 equip Na2CO3,
1.5 equip H2O, 3 h, 100 oC
1st use: >99% (GC yield)
2nd use: 91% (GC yield)
3rd use: 95% (GC yield)
4th use: 90% (isolated yield)
Scheme 4. Suzuki cross-coupling catalysed by the 14-Pd(II) xerogel

N
n
15a: R = CH2OCH3, n = 1
RO 15b: R = CH2CH3, n = 1
RO 15c: R = n-C6H13, n = 1
15d: R = n-C6H13, n = 2
n N
Figure 13. SEM image of the 15a-Cu(I) xerogel [62].
Table 9. Huisgen 1,3-dipolar cycloaddition catalysed by the 15–Cu(I) xerogels.
15-Cu(I) xerogel
N3 (1 mol %) N
+ R R
1.2 equip H2O, RT, air N N
Entry R Catalyst Time/h Yield/%

1 Ph 15a–Cu(I) 18 78
2 Ph 15b–Cu(I) 18 73
3 Ph 15c–Cu(I) 18 100
4 Ph 15c–Cu(I) 8 97
5 Ph 15d–Cu(I) 18 97
6 p-Tol 15c–Cu(I) 18 95
7 m-Tol 15c–Cu(I) 18 100
8 2-Py 15c–Cu(I) 18 100
9 TMS 15c–Cu(I) 18 12
10 n-Bu 15c–Cu(I) 18 8
Bian and Gao et al. investigated chiral binaphthylbisbipyridine-based copper(I)

coordination polymer gels [62]. Equimolar 15a-d and Cu(MeCN)2BF4 in hot MeCN-CH2Cl2,
MeCN-THF, or MeCN-dioxane (v/v, 1/1) form gels on cooling to RT. SEM revealed that the
existence of nanofibres are responsive for the gelation (Figure 13). Formation of 1D
coordination polymer of tetrahedral Cu(I) ions and the ligands at a ratio of 1:1 is necessary for
the gelation as indicated by 1H NMR, UV-vis and CD spectroscopy. DSC analysis showed
the 15a-Cu(I) gel has no endothermic transition up to 100 oC. π-π stacking interaction
between the 1D coordination polymers was revealed by UV-vis spectroscopy. Cu(I) is
significantly stabilised by the gel network with an increase of 1.20 V for the redox potential
of Cu(I)/Cu(II) of 15c-Cu(I) compared to Cu(I)(2,2'-bipyridine)2. The catalytic activity of the
15–Cu(I) xerogels was explored in the Huisgen 1,3-dipolar cycloaddition (“click” reaction)
(Table 9). The 15c–Cu(I) xerogel gave optimal result in the reaction of benzyl azide and
phenylacetylene with quantitative conversion in water at RT. The xerogel catalyst can be
easily separated from the reaction mixture, and the recovered catalyst could be used for
consecutive reaction for three times without significant loss of activity.
3. CATALYSIS BY POST-MODIFIED GELS

Loading of catalytically active centres to a preformed functionalised organogel or
metallogel is another strategy to produce a gel catalyst. Miravet and Escuder reported
pyridine-functionalised organogels. Dipyridine ligands based on amide linkages with
stereospecific attachment of isopropyl groups, 16a and 16b, efficiently gel H2O and a variety
of organic solvents including toluene (Scheme 5) [63]. Intermolecular mutiple H-bonding
similar with that present in 7c is the driving force for gelation. The toluene gels could be post-
modified by complexation of Pd(II) ions to from Pd-N(pyridine) coordination bond for
catalytic activity. A solution of Pd(OAc)2 in toluene was layered on top of the gel and was
observed to diffuse into it. Evidence for incorporation of palladium into the actual fibres of
the gel was obtained from TEM, since no metal shadowing was required to image these fibres
(Figure 10). Metal-complexation could help reinforce H-bonding organogel fibres to obtain
mechanically robust gels. The Pd(II)-immobilized gel showed catalytic activity for the
oxidation of benzyl alcohol to benzaldehyde at 65 oC with a maximum yield of 50% (10
turnover numbers) after 48 h.
O H H O O O
H H
N N N N N N
N N
H O O H H H
N N N O O N
16a 16b
16-Pd(II) gel (5 mol %) CHO

OH
toluene, air, 65 oC, 48 h
Scheme 5. Aerobic oxidation of benzyl alcohol catalysed by the 16-Pd(II) gels.
A very simple method for formation of a coordination polymer gel involves reaction
between Fe(NO3)3·9H2O and the 1,3,5-benzentricarboxylic acid (H3BTC) in ethanol [64]. The
gel forms within a few minutes, is stable to a range of solvents but dissolves in aqueous
hydrochloric acid. The Fe3+ gel is potentially useful since it also forms in the presence of
methylmethacrylate, which can be polymerised to give PMMA and the gel template removed
with aqueous HCl. This leaves the organic polymer imprinted with the original gel structures.
Accordingly SEM showed this PMMA to have a sponge-like structure with pores in the size
range 1-10 μm (Figure 15). With the gel as template, macroporous poly(glycidyl
methacrylate-co-ethylene glycol dimethacrylate) was fabricated to show promise in
chromatographic separation of protein [65]. Recently, Kaskel et al. investigated the
adsorption properties of the Fe(III)-carboxylate gels. Their aerogels have highly porous nature
with a combination of micro- and macroporosity (total pore volume 5.62 cm3 g-1 and BET
surface area 1618 m2 g-1), which are promising as catalysts or catalyst supports [66].
Figure 14. TEM images of the xerogels of 16b before modification with Pt-shadowing (A) and after
modification with Pd(OAc)2 with no shadowing (B, C) [63].
Figure 15. SEM images of spongelike PMMA templated by the Fe(III)-BTC gel [64].
1778 Jianyong Zhaang and Stuart L. James
H
HOOC CO
OOH HOOC
N
PPh2
N
H
HOOC COOH H
H
HOOC HOOC
17a H3BT
TC 17b
Sccheme 6. Bridging carboxylatee acids for metaallogels.
For catalyssis, the Fe-BT TC gel has been

b modifiedd with differeent functional groups to
obbtain a ran nge of funcctionalised Fe-gels
F basedd on dicarbboxylic acid, e.g. 5-
diiphenylphosphhanylisophthaalic acid (17aa, Scheme 6)) [67]. Gels could be forrmed when
m
mixing of the solutions of 17a and Fe((NO3)3·9H2O in alcohols and a DMF. SE EM of the
xeerogels revealled globular orr block-like morphologies
m o 2-10 μm foorming an inteerconnected
of
poorous network k (Figure 16aa,b). The phoosphine-functiionalised gel with phosphoorus donor
avvailable for fuurther coordinnation has proomising catalyytic applicationns for post-mmodification
w catalyticallly active centtres. After loaading of Pd(II)), the gel show
with wed efficient catalysis
c in
thhe Suzuki–Miiyaura cross–coupling of aryl a halides/bbromopyridinees with variouus boronic
accids under ammbient atmospphere (Table 10).1 The phossphine gel shoows potential to act as a
neew type of funnctionalisable porous scaffoold, and the geel could be eassily recovered and reused
foor subsequentt reactions, e.g. the couplling of 4-bromopyridine with w 3,5-difluuorophenyl-
booronic acid.
a b
c d
Fiigure 16. SEM and TEM images of the Pd(II) modified 17a––Fe(III) (a,b) annd 17b–Fe(III) (c,d)
xeerogels [67,68]..
Table 10. Suzuki–Miyaura cross–coupling of aryl halides/bromopyridines with boronic

acids catalysed by the Pd(II) modified 17–Fe(III) gels.
17-Fe(III)Pd(II) gel
(0.5 mol %)
R X + B(OH)2 R
3 equip Na2CO3
X = I, Br 1.5 equip MeOH, 60 oC
Entry Catalyst X R Time/h Yield/%

1 17a-FePd gel I H 1.0 100
2 17a-FePd gel Br H 0.5 71
3 17a-FePd gel Br OMe 1.0 35
4 17a-FePd gel Br COCH3 1.0 99
5 17b-FePd gel I H 0.5 >99
6 17b-FePd xerogel I H 0.5 >99
7 17b-FePd gel Br H 0.25 91
8 17b-FePd gel Br COCH3 0.5 >99
9 17b-FePd gel Br OCH3 0.5 72
10 17b-FePd xerogel Br OCH3 1.0 69
11 17b-FePd gel Cl H 11 46
12 17b-FePd xerogel Cl H 0.5 8
13 17b-FePd gel Cl COCH3 1.0 14
14 17b-FePd xerogel Cl COCH3 3.0 12
B(OH)2 N
N 17-Fe(III)Pd(II) gel
(0.5 mol %) R
+
Br 3 equip Na2CO3
R R
MeOH, 60 oC
PyBr R
Entry Catalyst PyBr R Time/h Yield/%

15 17a-FePd gel 4-bromopyridine F 2.0 95
16 17a-FePd gel 4-bromopyridine H 1.0 >99
19 17b-FePd gel 4-bromopyridine Me 1.0 >99
20 17b-FePd xerogel 4-bromopyridine Me 1.25 >99
21 17b-FePd gel 3-bromopyridine Me 0.5 >99
22 17b-FePd xerogel 3-bromopyridine Me 2.0 77
23 17b-FePd gel 2-bromopyridine Me 6.0 86
24 17b-FePd xerogel 2-bromopyridine Me 1.0 30
25 17b-FePd gel 4-bromopyridine F 3.0 58
26 17b-FePd gel 3-bromopyridine F 27 93
27 17b-FePd xerogel 3-bromopyridine F 5.0 8
28 17b-FePd xerogel 2-bromopyridine F 2.0 16
The coordination bond (e.g. Fe-N bond) present in metallogels has been employed to
immobilise active catalysts resulting from the dynamic nature [68]. A bifunctional ligand, 5-
1H-benzo[d]imidazole-1,3-dicarboxylic acid (17b, Scheme 6), forms coordination polymer
gels with Fe3+ in DMF-H2O, DMF, and DMF-MeOH. The xerogels have an interconnected
porous network of globular nanometer-sized particles of ca. 100 nm, as indicated by SEM and
TEM (Figure 12c,d). In the gels, the hard metal ion Fe3+ strongly coordinates to carboxylate
groups to form the gel network, and Fe3+ may also coordinate to the imidazole group less
strongly. When Pd2+ is loaded, binding of softer Pd2+ via the imidazole N atom is more
favourable resulting in cleavage of Fe–N(imidazole) bond and generation of new Pd–N bond
due to their different binding ability. Compared with its homogeneous analogue, the Pd(II)-
modified coordination polymer gel exhibited significantly improved activity in the Suzuki–
Miyaura cross–coupling (e.g. coupling of phenylboronic acid and 4-bromoanisole), and could
be reused for several times (Table 10).
CONCLUSION
Gels are a type of aggregates between highly ordered aggregates (crystals) and random
aggregates (amorphous solid). Its particular complexity of gels has been shown in literature.
The actual molecular structures of most gels are still beyond current techniques. The results
of crystal engineering help understand the structure of gel network, but it is still far from the
final structure. Supramolecular interactions between gelators, between liquids, and between
gelator and liquid have not been fully understood yet. The rational design, especially of
catalytic gelators, is still in infancy.
As shown above, supramolecular gels provides an interesting, useful and increasingly
important medium in which to investigate and exploit catalytic chemistry, and indeed the
chemistry and physics of active catalytic centres in general. The examples described in the
chapter demonstrate that unique new catalytic properties can arise from combining gels with
catalytically active centres. In some cases supramolecular gels show enhanced activity
compared with their homogeneous analogues, as already noted. With the ever-present need
for ‘enabling materials’ for current and future technological needs, one can be optimistic that
further catalytic applications may follow since catalytic supramolecular gels are clearly
synthetically available and they display unusual catalytic properties.
ACKNOWLEDGMENT
We gratefully acknowledges the Natural Science Foundation of China (NSFC) (Grants
No. 20903121), the Specialized Research Fund for the Doctoral Program of Higher Education
of China, the Fundamental Research Funds for the Central Universities, and the SRF for
ROCS, SEM, for financial support.
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Chapter 6
GLYCEROL AS A SUSTAINABLE SOLVENT

FOR HOMOGENEOUS CATALYSIS
Adi Wolfson*, Christina Dlugy and Dorith Tavor

Green Processes Center, Chemical Engineering Department, Sami Shamoon
College of Engineering, Bialik/Basel Sts. Beer-Sheva, 84100 Israel.
ABSTRACT
With its promising physical and chemical properties, glycerol can be used as a
sustainable solvent in many catalytic and non-catalytic organic reactions. Polar and non-
toxic, glycerol is a biodegradable, recyclable liquid that is manufactured from renewable
sources and that facilitates the dissolution of organic substrates, inorganic compounds,
and transition metal complexes. Glycerol also enabled easy isolation of the reaction
product either by extraction with glycerol immiscible solvents such as diethyl ether, ethyl
acetate, and supercritical carbon dioxide or through distillation. Using glycerol as a
solvent also enabled catalyst recycling, emulsion-like systems, and microwave-promoted
reactions. Furthermore, in many reactions, the use of glycerol as a solvent promoted
improved activities and selectivities of the reactants. In addition, in certain reactions such
as the catalytic transfer-hydrogenation of various unsaturated organic compounds and the
transesterification of alcohols, glycerol was used as both solvent and reactant.
Keywords: Glycerol, sustainable solvent, catalysis, homogeneous catalysis, green chemistry,

catalyst recycling.
1. INTRODUCTION
The need for an efficient, low energy, and clean (i.e., "greener") industrial process in
which energy and waste are minimized and costs are reduced is of universal concern.
Solvents are used daily in innumerable industrial processes as reaction mediums, in
*
Corresponding author. Email: adiw@sce.ac.il.
186 Adi Wolfson, Christina Dlugy and Dorith Tavor
separation procedures, and in dilutions. The chemical, physical, and biological natures of a
solvent are of paramount importance in any process that involves mass, heat, or momentum
transfer [1, 2]. Safety and the environment are also primary concerns in the selection of a
solvent [3, 4]. As such, using a biodegradable solvent from a renewable resource such as
plants is preferable. In addition, the chosen solvent should have minimal volatility and it
should be chemically and physically stable, recyclable, and reusable. When a solvent is used
as part of the reaction media, the solubilities of the reactants (gases, liquids, and solids) must
be taken into account. The chemical composition of the solvent can also affect reaction
activity and selectivity, and its physical properties may dictate the reaction conditions [5].
Organic chemistry is typically carried out in solution to dissolve reactants and/or
homogeneous catalysts and usually requires large amounts of solvent [5]. Traditionally
employed in the majority of chemical processes, petrochemical solvents have severe
implications for the environment. Hence the search for environmentally friendly reaction
mediums is of primary interest. Catalysis also plays an important role in the prevention of
waste generation in organic synthesis [6-8], as it combines several transformations into single
steps. In some reactions, catalysis can eliminate the need for toxic reagents. Furthermore,
improving reaction selectivity in catalytic processes helps reduce the formation of by-
products and thus leads to simpler, cleaner, and more effective separation processes [9-12].
Moreover, catalytic reactions are usually performed under milder conditions resulting in
lower energy consumption.
Solvent characteristics also dictate the most effective separation method for product
recovery [13]. The ease with which the product can be separated from the costly soluble metal
catalyst for the latter to be recycled is often the determining step for large-scale
implementation. A solvent with a relatively high boiling point would allow distillation of
more volatile products, but when large organic products are involved, distillation is usually
not applicable. In addition, the harsh conditions often present during product distillation may
lead to product or catalyst decomposition. Extraction of the products using an additional
solvent, which would form a two-phase (biphasic) system with the reaction solvent, is a
feasible alternative. Although commonly used to recycle catalysts [11], many biphasic
catalytic systems, either reaction or extraction, suffer from cross-contamination of the liquid
phases, an undesired result that necessitates additional downstream separation. The ideal
system for simple separations without the addition of an extraction solvent, therefore, would
involve substrates that are fully or partially miscible in the reaction phase and products that
are poorly miscible. When the addition of an extraction solvent is necessary, the reaction
solvent should be immiscible with a variety of other solvents. Furthermore, extraction solvent
selection should also be based on how it affects the environment, worker safety, and the ease
of subsequent separations.
Alternative Reaction Media
Reaction solvent suitability also depends on, in addition to its solubility and
environmental friendliness, whether it promotes easy product separation and catalyst
recovery, i.e., whether it is a sustainable solvent. A variety of environmentally benign solvent
alternatives has been proposed in the literature, including water, ionic liquids, fluorous
solvents, and supercritical fluids. Water, with its ideal environmental impact, relatively low
Glycerol as a Sustainable Solvent for Homogeneous Catalysis 187
price, and reasonable boiling temperature, is an attractive solvent, but the negligible solubility
of many organic compounds in water can cause low reaction rates [14]. Moreover, the water
crisis currently facing the entire planet is liable to increase the price and decrease the
availability of water for industrial applications. Water-organic biphasic systems were thus
employed to solve solubility limitations and to recycle transition metal complexes (TMCs).
However, reactions run in biphasic systems are usually accompanied by mass transfer
limitations.
Organic and catalytic reactions in mixtures of paraffin with fluorinated solvents have also
been reported in the literature [15, 16]. In these systems, the reaction is single phase if
performed at the reaction temperature while a temperature decrease leads to a two-phase
system. Although this system enables the TMCs to be separated and recycled, they must
undergo tedious modification prior to their use in the reaction. Furthermore, solvent
decomposition at high temperatures may yield hazardous compounds.
Recently, increasing attention has been focused on ionic liquids (ILs) as alternative green
solvents due to their unique and versatile physical and chemical properties [17-20]. Ionic
liquids are organic salts that are liquid near ambient conditions (Tm < 100 °C). Composed of
ions, they have negligible vapor pressure and thus do not contribute to airborne pollution. ILs
have already been used in numerous mono- or biphasic catalytic systems in a variety of
organic reactions with and without TMCs and enzymes. Separation of the products and
recycling of the catalyst were accomplished by distillation or extraction with a non-miscible
solvent.
Nevertheless, the widespread use of ILs as reaction media has been thwarted by their
considerable drawbacks. The relatively high price of most ILs will prevent them from being
used as solvents in large-scale processes, even though they can be recycled and re-used.
While ILs are potentially green, mainly due to their low vapor pressure, their chemical and
physical properties and toxicology and safety measurements are not completely known [21,
22]. In addition, some ionic liquids have low biodegradability, and large amounts of
hazardous and volatile organic solvents are utilized in their production.
Supercritical and compressed fluids—especially supercritical carbon dioxide (scCO2)—
represent another potential class of green solvents. Supercritical fluids are substances above
their critical temperature and pressure [23-25] and represent a highly tunable solvent class.
Because supercritical fluids are extremely sensitive to pressure and temperature, large
changes in properties like density, viscosity, diffusivity, and thermal conductivity, to name
but a few, are possible. This sensitivity allows for the precise selection of the desired
properties for any given reaction with supercritical fluids, and, as such, compressed fluids
represent many solvents in one compound.
CO2 from non-sequestered sources represents an environmentally benign and non-toxic
solvent for reaction, extraction, and material processing [26-29]. Its relatively low critical
pressure and temperature (Tc=31°C, Pc= 74 bar) together with its low toxicity and
environmental impact and affordable price make it an even more attractive solvent candidate.
Used for years for analytical or extraction purposes, scCO2 is now widely used in extraction
and purification processes in the petrochemical, food, and pharmaceuticals industries [30, 31].
Supercritical fluids, especially scCO2, have also been reported as green solvents for catalysis.
The reactants and catalysts with specialized ligands are in one homogeneous phase. CO2 can
be miscible with reaction gases (e.g., H2, O2, CO, etc.), a characteristic that can completely
eliminate common interfacial mass transfer limitations. In addition, separations can be
achieved via changes in the temperature or pressure. However, it is often difficult or

uneconomical to render reactants, products, and especially metal complex catalysts soluble in
the supercritical fluid phase.
Based on the above-mentioned specifications for an environmentally friendly solvent,
glycerol (glycerin, 1,2,3-propanetriol), widely available and inexpensive, has a high potential
of fulfilling the requirements of a green solvent. Glycerol is the main by-product from the
conversion of oils and fats in oleochemical production (Figure 1) [32, 33]. In the past decade,
its price has substantially decreased due to an increase in supply from the production and use
of fatty acid derivatives in the food, cosmetics, and drugs industries and in biofuel synthesis,
i.e., biodiesel. Indeed, the biodiesel market is growing rapidly as it is sulfur- and aromatics-
free and since it is obtained from renewable resources.
ROCOR1
OCOR1 OH
Catalyst
+
OCOR2 + 3 ROH ROCOR2 + OH
+
OCOR3 OH
ROCOR3
Triglyceride Alcohol Mixture of Glycerol
alkyl esters
Figure 1. Transesterification of triglycerides.
A non-toxic, biodegradable, and recyclable liquid that is highly inert and stable, glycerol
is compatible with many other chemical materials. These qualities make it suitable for use as
a humectant, plasticizer, emollient, thickener, dispersing medium, lubricant, sweetener,
bodying agent, antifreeze, and processing aid. As such, glycerol has been approved for food
and drug use by many government agencies (US FDA, etc.) and is used as an ingredient or
processing aid in cosmetics, toiletries, personal care, drugs, and food products. In addition,
glycerol derivatives such as glycerol esters are also extensively used in many industries.
Glycerol also forms the raw material in chemical syntheses [34] such as the production of
dendrimers and hyperbranched polyethers and polyesters [35], catalytic hydrogenolysis to
propylene glycols (especially 1,3-propanediol, which is a high value chemical in the synthesis
of polyesters [36, 37]), and catalytic oxidation to form various commercially important
compounds such as dihydroxyacetone and glyceraldehydes [38]. Used as an energy source for
microorganism fermenting systems, glycerol yielded ethanol and hydrogen [39]. However, in
all applications, whether as a reactant or as an additive, glycerol is used principally as a
highly refined and purified product. And as increasingly greater quantities of glycerol are
generated by the biodiesel industry, economical ways of glycerol utilization must be explored
to further defray the cost of biodiesel production.
In this review we will explore the scope and limitation of using glycerol as a sustainable
reaction medium in organic transformations.
2. GLYCEROL AS A SUSTAINABLE REACTION MEDIUM

Glycerol's physical and chemical properties hint at its promise to be used as a green
solvent. It has a very high boiling point and negligible vapor pressure, it is compatible with
most organic and inorganic compounds, and it does not require special handling or storage.
Like other polar organic solvents such as DMSO and DMF, glycerol dissolves inorganic salts,
acids and bases, enzymes and TMCs, but it also dissolves organic compounds that are poorly
miscible in water and it is non-hazardous. Hydrophobic solvents such as ethers and
hydrocarbons, which are immiscible in glycerol, enable reaction products to be simply
extracted. Product distillation is also feasible due to the high boiling point of glycerol. A
comparison of several relevant properties of glycerol, water, ionic liquid [1-butyl, 3-
methylimidazolium hexafluorophosphate (BmimPF6) as a representative commercial and
commonly used IL], and perfluorohexane (tetradecafluorohexane) as the representative
fluorocarbon solvent are summarized in Table 1.
Table 1. Properties of alternative green solvents [40]
Glycerol H2 O BmimPF6a C6F14

NBP(°C) 290 100 >300 58-60
Vapor pressure at 50°C <1 92.51 <1 n.a.
(mmHg)
Dielectric constant (25°C) 42.5 78.5 11.4 <5
Viscosity (cP) (30°C) 629 1 312 n.a
Density (g/mL) 1.29 1 1.37 1.66
Biodegradability Yes - No No
LD50 (Oral-Rat) (mg/Kg) 12600 >90000 ~1500 ~5000
TMCs modification Without/ Minor Without Tedious
minor
a
BmimPF6= 1-butyl-1-methylimidazolium hexafluorophospate.
In addition to the characteristics that confer upon glycerol its potential for use as a green
reaction medium, it boasts additional properties that grant it superiority over alternative green
solvents. First, because glycerol is produced as a by-product of the constantly expanding oil-
based chemical industries, its availability is high and its price is low. In addition, the
production of glycerol is a simple transesterification (Figure 1) process that is not associated
with the use of a toxic reagent or the production of large amounts of toxic waste as with other
green solvents. In short, its unique chemical, physical, and biological properties make
glycerol an exceptionally safe solvent.
Based on all the advantages outlined above, Wolfson, Dlugy, and Shotland reported
several years ago for the first time about the use of glycerol as a reaction medium in both
catalytic and non-catalytic organic syntheses [40]. Since then, glycerol has been successfully
employed as a green solvent in a wide variety of organic reactions and synthesis
methodologies, showing its versatility as a solvent for organic synthesis (Table 2). Indeed,
glycerol is suitable in homogeneous and heterogeneous chemo- and bio-catalyst systems as
well as in catalyst free systems, and in most of the reactions, high product yields and
selectivities were achieved.
Table 2. Organic reactions in glycerol
Entry Reaction Catalyst Reference

Non Catalytic
1 Nucleophilic substitution - 40
2 Reduction of carbonyls - 40, 43
3 aza-Michael reactions - 41
4 Michael reactions - 41
5 Ring opening of epoxide - 41
6 Electrophilic activation of aldehydes - 42
7 Wolff-Kishner reduction of benzaldehyde - 43
8 Electro reduction of benzaldehyde - 43
Homogeneous and heterogeneous chemo-catalysts
9 Heck coupling Pd(OAc)2 40, 44, 45
Pd(OAc)2(TPPTS)2a
PdCl2
PdCl2(TPPTS)2a
PdCl2(DPPF)2b
Pd/C
10 Suzuki coupling Pd(OAc)2 44
Pd(OAc)2(TPPTS)2a
PdCl2
PdCl2(TPPTS)2a
PdCl2(DPPF)2a
Pd/C
11 Aldol condensation KOH 45
12 Electrophilic substitution of indoles CeCl3*7H2O 46
13 Ring opening of epoxides Bases 47
14 Knoevenagel-type reactions Bases 47
15 β, β-diarylation of acrylates Pd/APc 48
16 Transfer hydrogenation-dehydrogenation Ru(p-cumene)Cl2-dimer 50, 51
RuCl2(TPPTS)3a
Ru/C
Pd/C
Raney-nickel
17 Hydrogenation RhCl2(TPPTS)3a 40, 43
Pd/C
18 Asymmetric reduction Ru-BINAP 43
19 Dimerization [C8Mim]NTf2d 41
20 Michael reactions KF/Alumina 52
Homogeneous and heterogeneous bio-catalysts
21 Asymmetric reduction Free and immobilized 40, 53, 54,
bakers yeast, 43, 55
Aspergillus terreus,
Rhizopus oryzae
22 Trans-esterification (kinetic resolution of Novozyme-435 40, 49
racemate)
a
TPPTS= tris-(3-sulfophenyl)-phosphine trisodium salt. b DPPF= [1,1'-Bis (diphenylphosphino)
ferrocene). c Pd/AP= palladium nanoparticles stabilized over sugar-based surfactant. d
[C8Mim]NTf2= 1-methyl-3-octyl imidazolium bis[trifluoromethylsulfonyl]amide.
Solubility of Reactants and Products in Glycerol
The key property of a reaction solvent is its solvation capability. A solvent should
facilitate the combination of reactants and catalysts, and as such, it should be able to dissolve
solids, liquids, and gases as required. Many organic reactions also require the dissolution of
salts and organic compounds or hydrophilic and hydrophobic molecules simultaneously. On
the other hand, the solubility of the reaction product in the reaction medium and the nature of
the solvent also dictate separation technique. Glycerol, a polar organic solvent, can dissolve a
variety of compounds, but it also facilitates the separation of many organic molecules by
simple extraction with glycerol immiscible solvents.
Several catalyst-free organic transformations were performed in glycerol using its ability
to dissolve both organic and inorganic molecules (Table 2, entries 1-8). Table 3 summarizes
the yields of several representative catalyst-free reactions in glycerol, water, or DMSO for
comparison and illustrates the beneficial use of glycerol as a reaction solvent. One of the first
examples of organic transformation in glycerol that exploits its ability to dissolve a non-polar
organic compound and a polar ionic salt together is the nucleophilic substitution of benzyl
chloride with potassium thiocyanate [40]. Similarly, the nucleophilic substitution of benzyl
bromide with ammonium acetate (Figure 2a) was run in water, DMSO, or glycerol, and the
reactions in both organic solvents were faster than that in water, since the solubility of benzyl
bromide, which is negligible in water, was augmented in the organic solvents (Table 3, entry
1). The yield of benzyl acetate in DMSO was higher then in glycerol, but as a natural,
biodegradable, green organic solvent, glycerol is preferable. Separation of product at the end
of the reaction was done by extraction with diethyl ether followed by evaporation of the
extracting solvent under reduced pressure [40]. It should be maintained that although the
addition of extraction solvent makes the procedure "less green", when glycerol is used, less
hazardous extraction solvents can be used because glycerol is immiscible with a variety
hydrophobic solvents.
Another example of the advantage of using glycerol (as a polar reaction medium) instead
of water and DMSO was demonstrated by Gu and Jérôme in the catalyst-free azo-Michael
reaction between p-anisidine and n-butyl acrylate (Figure 2b; Table 3, entry 2; [41]). The
reaction, which showed no product in the DMSO and only trace amounts of product in the
water, yielded large amounts of product in the glycerol. The authors assumed that the
different behaviors observed for water and glycerol arose from the better affinity of
p-anisidine for the glycerol interface, thus inducing a faster reaction rate compared to what
was observed with water. At the end of the reaction the product was removed by extraction
with ethyl acetate after which the glycerol was re-used twice. The second and third reaction
runs returned comparable product yields. Moreover, using crude glycerol from the
transesterification of oil (Figure 1), which produced about 20% water and soap, was also
tested in the same reaction and yielded similar amounts of product. Employing crude glycerol
as a solvent has definite environmental and economical advantages as it does not require
tedious purification after alcoholysis.
In the same report, Gu and Jérôme also studied the catalyst-free ring opening of styrene
oxide with p-anisidine (Figure 2c; Table 3, entry 3; [41]). In this reaction, which is usually
acid-catalyzed, the reaction in either water or glycerol proceeded successfully, even without a
catalyst. Moreover, in terms of selectivity, glycerol was also shown to perform well, as the
regioselectivity obtained in glycerol was higher than that for water.
Br OAc
a) + NaOAc + NaBr
NH2
H
O N O
b) + O O
MeO
OMe
H
N
OH
NH2
O MeO
a
c) +
OH
H
OMe N
MeO
b
H
N
CHO
d) + 2
N
H
NO2
N
H
Figure 2. Catalyst-free reactions in glycerol: a) Nucleophilic substitution; b) aza-Michael reaction [41];

c) Ring opening of styrene oxide [41]; d) Electrophilic activation of nitrobenzaldehyde [42].
The electrophilic activations of aromatic aldehydes were also reported to proceed better
in glycerol than in water or in different organic solvents (Figure 2d; Table 3, entry 4; [42]).
Again, reactions that usually include acid catalyst were run in glycerol under catalyst-free
conditions. In the reaction between 4-nitrobenzaldehyde and 2-methylindole, not only was the
product yield in glycerol higher than in water, but it also resulted in a glycerol insoluble solid
that was easily isolated by filtration.
The examples discussed above illustrate the flexibility of glycerol as a reaction solvent
that facilitates both the dissolution of a range of organic and inorganic compounds and simple
product separation. Furthermore, in addition to the green nature and production process of
glycerol compared to other green alternative reaction mediums, its use as a solvent also
permitted running several reactions without catalyst and yielded higher activities and
selectivities. The reaction procedure in glycerol is therefore cleaner as it is more material and
energy efficient.
Table 3. Catalyst-free organic transformations in polar solvents
Product yield (%)
Reaction Water DMSO Glycerol

Nucleophilic substitutiona 38.1 100 60.3
aza-Michaelb,[41] <5 0 82
Ring opening c,[41] 88 (a/b=76/24)d 0 85 (a/b=93/7)d
Electrophilic activation of
76 <5 95
aldehydese, [42]
a
Reaction conditions: 0.8 mmol benzyl bromide, 0.88 mmol ammonium acetate, 5 ml solvent, 70 °C, 1
h. b Reaction conditions: 1.0 mmol p-Anisidine, 1.0 mmol, butyl acrylate, 1 mL solvent, 100 °C, 20
h. c Reaction conditions: 1.0 mmol p-Anisidine, 1.0 mmol butyl acrylate, 1 mL solvent, 100 °C, 20
h. d Regioselectivity as presented in Figure 2c.e Reaction conditions: 90 °C, 3 h.
Heterogenization of Metal Catalysts in Glycerol
Catalysts are required for many organic reactions to proceed. In fact, the development of
environmental friendly processes often rely on catalysis, the inclusion of which may enable
toxic reagents to be replaced and may improve reaction activity and selectivity. As a result,
the formation of by-products can be reduced, leading to simpler, cleaner, and more effective
separation processes [6-9]. Heterogeneous catalysts have the distinct advantage that they can
be easily separated and re-used while homogeneous catalysts are usually very specific, active,
and selective. Therefore, TMCs in biphasic systems are frequently heterogenized to combine
the advantages of homogeneous and heterogeneous catalysis [11].
X
Pd catalyst, base R
+ R + HX
a) Glycerol
X=Br, I
X B(OH)2
b) Pd catalyst, base
+
Glycerol
X=I, Br, Cl
Figure 3. a) Heck coupling of halobenzene and activated olefin; b) Suzuki cross-coupling of

halobenzene and phenylboronic acid [44].
A variety of catalytic reactions were run in glycerol using homogeneous and

heterogeneous chemo- and bio-catalysts (Table 2, entries 9-22). One of the first examples of a
catalytic reaction in glycerol was the palladium-catalyzed Heck C-C coupling reaction of
iodobenzene and butyl acrylate (Figure 3a; [40]). A more intense study of the scope and
limitations of C-C coupling in glycerol was reported later for both the Heck coupling of
halobenzenes with various alkenes and the Suzuki cross-coupling of halobenzenes with
phenylboronic acid (Figure 3a and b; [44]). Palladium salts and complexes and supported
palladium catalyst were used together with organic and inorganic bases as co-catalysts (Table
4). In general, it was found that glycerol can function as an alternative green solvent for the
C-C coupling reactions. Various halobenzenes can be employed and as expected,
iodobenzene was the most active halobenzene. The use of palladium salts and complexes as
catalysts and inorganic bases as co-catalysts yielded more products (Table 4).
Table 4. Palladium-catalyzed Heck and Suzuki coupling of iodobenzene with butyl

acrylate and phenylboronic acid in glycerola [44]
Entry Catalyst Base Time Yield (%) Time Yield (%)

(h) Heckb (h) Suzukic
1 PdCl2 Et3N 4 74 1 76
2 PdCl2 Na2CO3 4 100 1 90
3 Pd(OAc)2 Et3N 4 65 1 81
4 Pd(OAc)2 Na2CO3 4 72 1 95
5 PdCl2(TPPTS)2 Et3N 4 87 1 83
6 PdCl2(TPPTS)2 Na2CO3 4 100 (83)d 1 94
7 Pd(OAc)2 Et3N 4 56 1 66
(TPPTS)2
8 Pd(OAc)2 Na2CO3 4 100 1 75
(TPPTS)2
9 PdCl2(DPPF)2e Na2CO3 4 86 1 82
10 Pd/C Et3N 4 40 1 61
11 Pd/C Na2CO3 4 78 1 88
a
0.5 mmol iodobenzene, 0.75 mmol butyl acrylate or phenylboronic acid, 0.01 mmol catalyst, 0.6
mmol base, 5 g glycerol, 80 °C. b 4 h. c 1h. d Styrene was employed instead of butyl acrylate. eAs
above, but using 20 g glycerol.
As a sustainable solvent, glycerol also enabled both solvent and catalysts to be recycled
[40, 44]. The recycling of transition metal complexes of the types PdCl2(TPPTS)2 and
PdCl2(DPPF)2 (DPPF= [1,1'-Bis (diphenylphosphino) ferrocene) and the supported palladium
catalyst (Pd/C) in glycerol was examined in the Suzuki cross-coupling of iodobenzene and
phenylboronic acid (Figure 3b; Table 5; [44]). Catalysts were recycled after the extraction of
both iodobenzene and biaryl from the glycerol catalytic phase using diethyl ether. Then, equal
amounts of fresh substrates and sodium carbonate were added to the glycerol, and the
reactions were re-run under identical conditions. The activity of PdCl2(DPPF)2 was not
reduced after each cycle while those of PdCl2(TPPTS)2 and Pd/C were (Table 5). In the case
of PdCl2(TPPTS)2, the authors assumed that the reduction in its activity may have resulted
from the decomposition of the complex, as the formation of palladium aggregates was
observed.
As previously mentioned, glycerol synthesis via alcoholysis yielded crude glycerol with
alcohol, water, and soap as leftovers. Yet when glycerol is used as a reactant or as an additive,
usually it must be in its highly refined and purified form. The tedious purification process
may be avoidable, however, if non-purified, crude glycerol is used as the reaction medium.
Therefore, crude glycerol from several oil sources and without any purification was also
tested as a reaction medium in the palladium-catalyzed Heck coupling of iodobenzene and
butyl acrylate using various catalysts (Figure 3a; Table 6; [44]). The reaction was compared
to those in pure glycerol and in pure glycerol with the addition of methanol and water to
resemble crude glycerol contaminates (Table 4). In general, although it was found that the
crude glycerol yields were lower than those in pure glycerol with all the catalysts tested, they
were still satisfactory. In addition, for more stable complexes, as in the case of
PdCl2(TPPTS)2, the conversion in crude glycerol was close to that of the reaction in pure
glycerol (Table 6, entry 3).
Table 5. Catalyst recycling in the Suzuki cross-coupling of iodobenzene and

phenylboronic acid in glycerola [44]
Yield (%)
Catalyst /Cycle PdCl2(TPPTS)2 Pd/C PdCl2(DPPF)2b
1 88 98 82
2 55 61 80
3 47 50 80
a 0.5 mmol iodobenzene, 0.6 mmol phenylboronic acid, 0.6 mmol Na2CO3, 2 mol% palladium, 5 g
glycerol, 80 °C, 1h. b 20 g glycerol.
Table 6. Conversions of iodobenzene in the palladium-catalyzed Heck coupling of

iodobenzene and butyl acrylate in crude glycerola [45]
Entry Catalyst Pure Pure Pure Crude glycerol Crude glycerol

glycerol glycerol+ glycerol+ without the with the
methanolb waterb addition of addition of
KOH KOHc
1 PdCl2 94.2 96.1 97.2 58.5 63.6
2 Pd(OAc)2 70.1 70.8 71.2 41.3 45.7
3 PdCl2(TPPT 86.1 85.9 86.5 76.4 78.8
S)2 (73)d
4 Pd/C 75.4 77.6 77.2 39.0 47.8
a
Reaction conditions: 5 mL glycerol, 0.5 mmol iodobenzene, 0.6 mmol butyl acrylate, 80 °C, 4 h. b
Addition of 0.25 g methanol or water. c Addition of 0.5 mmol KOH. d Before the reaction, pure
glycerol was mixed with methyl esters of fatty acid.
To test whether leftovers from crude glycerol synthesis caused the reduced performance,
small amounts of methanol, water, or methyl esters of fatty acids were added to the pure
glycerol during the reaction. It was found that while the addition of either methanol or water
did not affect reaction conversions, the addition of fatty acid esters, i.e. biodiesel, to pure
glycerol resulted in a lower conversion (Table 6, entry 3). The authors mentioned that since
the palladium-catalyzed Heck coupling of halobenzene and activated olefin involved

coordination of a double bond of an olefin to the catalyst, it is possible that the biodiesel and
the soap traces in the crude glycerol coordinated to the catalyst and decreased its activity.
Nevertheless, as crude glycerol was produced by the alcoholysis of triglyceride in the
presence of KOH—which can also serve as co-catalyst in Heck coupling—the reaction was
run with and without the addition of extra KOH. Similar conversions with both reactions,
revealing that the residual base from the synthesis of crude glycerol can be re-used in the
Heck reaction (Table 6).
Crude glycerol from several oil sources was also used as a reaction medium in the aldol
condensation of n-valeraldehyde (Figure 4; Table 2, entry 11; [45]), using fresh or residual
KOH from alcoholysis as a catalyst. As expected, the condensation occurred with or without
the addition of excess base. The reactions run without the extra addition of fresh KOH yielded
lower conversions, probably since some of the KOH was lost and deteriorated during the
alcoholysis of the oil. In addition, it was found that the oil source did not affect reaction
performances [45]. Finally, the glycerol and the soluble base within were also successfully
recycled by extraction of the product with diethyl ether and the addition of fresh substrate.
O O H
KOH
2
H 800C, 2h H
Conversion with the addition of KOH: 43%

Conversion without the addition of KOH: 28%
Figure 4. Aldol condensation of n-valeraldehyde [45].
Another example of a recyclable catalytic system involving glycerol entails the use of
CeCl3*7H2O in indole reactions with aliphatic and aromatic aldehydes (Figure 5; Table 2,
entry 12; [46]). A variety of bis(indolyl)methanes were synthesized in good to excellent
yields and the glycerol and catalyst mixture was re-used up to five times after extraction of
the product with ethyl acetate without special treatment, and comparable yields were
produced during each subsequent synthesis.
CeCl3*7H2O
2 + RCHO
X X
NH 750C, 1.5-10h
X NH NH
X=H, Br
R=Aliphatic, aromatic 70-95% yield
Figure 5. Synthesis of bis(indolyl)methanes [46].

Emulsion Catalytic Systems in Glycerol
The high polarity of glycerol enabled the products to be easily isolated and the catalyst to
be easily recycled by extraction with hydrophobic organic solvents like ethers and esters. Yet
the polarity of glycerol may also be a drawback when the reactants comprise highly
hydrophobic compounds, in which case biphasic systems may develop, resulting in mass
transfer limitations and lower activity. The addition of surfactant to the reaction mixture can
facilitate the mixing of the two phases to produce an emulsion-like system.
The catalytic hydrogenation of styrene (which has a low solubility in glycerol) using a
RhCl2(TPPTS)3 catalyst was studied in glycerol with and without the addition of surfactant
(Figure 6; Table 2, entry 17; [40]). The reaction without added surfactant was slower then that
in methanol under similar conditions, but the addition of Pluronic, a triblock copolymer
surfactant, increased the conversion by almost 40%, from 61% to 84%.
Rh(TPPTS) 3 Cl2
+ H2
80 0 C, 3h
Conversion without the addition of surfactant: 61%

Conversion with the addition of surfactant: 84%
Figure 6. Catalytic hydrogenation of styrene [40].
Karam and co-authors also demonstrated a noteworthy emulsion catalytic system in

glycerol (Table 2, entry 13; [47]) in their study of the base-catalyzed ring opening reaction of
epoxides (Figure 7). Initially, several conventional solid bases were employed as catalysts,
yielding full epoxide conversion after only 18 h and large amounts of by-product from the
epoxide-glycerol reaction. The authors assumed that the low activity was due to the low
solubility of the reactants, which have long hydrocarbon chains, in the polar glycerol catalytic
phase. Employing a new family of aminopolysaccharides (APs) as surfactants and catalysts
with basic characters led to a decrease in reaction time and yielded only trace amounts of by-
product from the epoxide-glycerol reaction. (Figure 7).
OH
O
( )9 ( )9
O
O O
( )9 + ( )9 Product ester
OH OH
O OH
( )9
Glycerol ether
Solid base: time=18 h, conversion=98%, selectivity (ester/ether)=80/15

Aminopolysaccharide (AP): time=3 h, conversion=98%, selectivity (ester/ether)=95/traces
Figure 7. Ring opening of epoxides [47].
The authors suggested that the use of APs allowed the organic substrates to diffuse better
in the glycerol phase by creating hydrophobic environments within the glycerol. Moreover,
they found that micellar catalysis in glycerol was superior to that in water as the emulsions
formed in glycerol were found to be unstable. As a result, rapid phase separation at the end of
the reaction allowed easy product extraction without the assistance of organic solvents. The
procedure was successfully used not only in the selective ring opening of epoxides with
carboxylic acids, but also in other base-catalyzed reactions in glycerol, such as Knoevenagel-
type reactions, Henry reactions, and Michael additions [47].
The same sugar-based surfactants (APs) were also used to stabilize palladium nano-
particles in the β, β-diarylation of acrylates (Figure 8; Table 2, entry 15; [48]). Typically, the
β, β-diarylation of acrylates is performed at high temperatures in organic solvents with high
boiling points, but a greener synthesis route is possible with glycerol because of its greater
environmental friendliness and because the reaction temperature can be reduced when using
glycerol [48]. However, the highly glycerol miscible reaction products are difficult to extract
using glycerol immiscible solvents. Furthermore, distillation of the glycerol is also not a
feasible option due to its high boiling point. Hence, scCO2, which was found to be soluble in
glycerol (glycerol is only negligibly soluble in scCO2), was tested as an extraction solvent. It
was found that at 50 °C, 250 bar, and with a scCO2 flow of 40 g min−1, the β, β-diarylated
products were cleanly and selectively recovered with a molar purity of 93% while the Pd/AP
remained in the glycerol phase.
O Pd/AP, NH3 Ar O
+ 2 Ar-I
OR 1200C Ar OR
70-90% Yield
Figure 8. β, β-diarylation of acrylates [48].
Microwave-assisted Synthesis in Glycerol
As a non-volatile, highly polar organic solvent, glycerol is also applicable in microwave-

promoted reactions. Based on the ability of the solvent to absorb microwave energy and
convert it into heat, microwave heating is a more efficient and energy saving alternative to
conventional heating [56, 57]. Polar solvents, especially those with hydroxyl substitution are
very attractive solvents for this purpose due to their high dielectric constants and high boiling
points. Hence, glycerol seems to be an excellent candidate for microwave-assisted reactions.
In addition, non-volatile up to very high temperatures, glycerol is superior to water and other
organic solvents typically used for this purpose.
The first example of a microwave promoted organic transformation in glycerol was the
Wolff-Kishner reduction of benzaldehyde to toluene (Figure 9; Table 2, entry 7; [43]). The
reaction, which was carried out in a domestic microwave at lower temperatures than under
conventional heating, was much faster, and it yielded full conversion and selectivity to
toluene. In addition, microwave-promoted heating was also reported to enhance C-C coupling
reactions [58]. Therefore, the Suzuki C-C cross coupling reaction in glycerol was also
performed under microwave irradiation in a domestic microwave (Table 7). The results
illustrated in Table 7 confirmed the assumption that glycerol can be used successfully as a
solvent in microwave-assisted reactions.
NH2
H O N
+ H2NNH2 + KOH
Yield=100%
Selectivity=100%
Figure 9. Microwave-promoted Wolff-Kishner reduction of benzaldehyde to toluene in glycerol [43].
Glycerol as Reactant and Solvent
In the above-mentioned reactions, glycerol was used as a sustainable solvent, where it

enabled the dissolution of both reactants and catalysts, enhanced reaction activities and
selectivities, facilitated easy separation of the products and recycling of the catalysts, and
supported more efficient heating. In addition to being a solvent, glycerol can also function as
a reactant. One example of such a system is the lipase catalyzed kinetic resolution of an ester
racemate in glycerol, for which the glycerol functioned as both solvent and resolving agent
(Table 2, entry 22; [40, 49]).
In another example, glycerol was used simultaneously as solvent and hydrogen donor in
the catalytic transfer-hydrogenation of various unsaturated organic compounds while
oxidizing to dihydroxyacetone (Figure 10; Table 2, entry 16; [50, 51]). The reduction of
unsaturated compounds in glycerol, previously studied in the presence of metal hydrides as
stoichiometric reductants (Table 2, entry 2; [40, 43]), yielded large amounts of waste that had
to be neutralized, thus making the reduction procedure less environmental friendly

and less attractive.
Table 7. Microwave-promoted Suzuki cross-coupling of iodobenzene and phenylboronic

acid in glycerola [44]
Entry Heating Time (min) Conversion (%)

1 oil bath 60 94
2 microwave 5 15
3 microwave 10 61
a
Reaction conditions: 0.5 mmol iodobenzene, 0.6 mmol phenylboronic acid, 0.6 mmol Na2CO3, 2
mol% palladium, 5 g glycerol, 80 °C, 4h.
Alternatively, the catalytic hydrogenation of several organic molecules (Table 2, entry

17; [40, 43]) as well as the enantioselective hydrogenation of ethyl acetoacetate over Ru-
BINAP in glycerol (Table 2, entry 18; [43]) were limited most likely by the low solubility of
molecular hydrogen in glycerol. On the other hand, using glycerol as the hydrogen source in a
transfer-hydrogenation system resulted in very high product yields, and glycerol was
dehydrogenated to dihydroxyacetone, a valuable intermediate in the production of many
chemicals [59, 60]. This new catalytic system did not produce large amounts of waste as with
the metal hydride, and unlike hydrogenation with molecular hydrogen, neither special
equipment nor precautions were necessary. Moreover, as was previously shown, glycerol also
enabled easy product separation and catalyst recycling.
CHO CH2OH
OH O
Ru(p-cumene)Cl2-dimer, KOH
a) + HO OH + HO OH
24 h, 700C
Yield=99%
CHO CH2OH
OH O
Pd/C
b) + HO OH
+ HO OH
5 h, 700C
Yield=100%
CHO CH2OH
OH O
Raney Nickel, NaOH
c) + 3 HO OH + HO OH + 2 H2O
24 h, 700C
Yield=43%
Figure 10. Transfer-hydrogenations of unsaturated organic compounds in glycerol [50].

CONCLUSIONS AND PERSPECTIVES

Glycerol was found to be attractive as a sustainable solvent for organic reactions. A by-
product of fatty acid ester production from renewable sources, glycerol can be used as a
solvent without purification. It has promising physical, chemical, and biological properties
that make it non-volatile, non-hazardous, recyclable, and biodegradable, i.e., it is a green
solvent. In addition, glycerol can dissolve many organic and inorganic compounds and
transition metal complexes while also allowing easy product separation by extraction with
glycerol immiscible solvents such as ethers, esters, and supercritical carbon dioxide. Glycerol
was successfully used as a solvent in many catalytic and non-catalytic organic reactions,
using homogeneous and heterogeneous chemo- and biocatalysts. In many reactions, the
presence of glycerol as a solvent improved product yields and selectivities and enabled
catalyst recycling, emulsion-like systems, and microwave promoted reactions. Furthermore,
its high boiling point and polarity make glycerol the perfect candidate for non-conventional
heating and mixing reactions such as the microwave-assisted reaction. Finally, glycerol can
also be used as both solvent and reactant, such as in the catalytic transfer-hydrogenation of
various unsaturated organic compounds and in the transesterification of alcohols.
Despite glycerol's promise as a sustainable solvent for liquid phase catalytic and non-
catalytic organic syntheses, there are several drawbacks to its utilization, including the low
solubility of highly hydrophobic compounds in glycerol, the low solubilities of gases such as
hydrogen and oxygen in glycerol that limit its applications in catalytic hydrogenation and
aerobic oxidation, and the use of hazardous, hydrophobic organic solvents for product
extraction and catalyst recycling. These weaknesses should be further studied with the aim to
provide novel solutions. In addition, the effects of glycerol itself and of contaminants from its
production process on reaction performance should also be explored further.
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Chapter 7
HOMOGENEOUS CATALYSIS IN CARBONYLATIVE

COUPLING REACTIONS
Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage*

Department of Chemistry, Institute of Chemical Technology, N. Parekh Marg,
Matunga, Mumbai-400 019. India.
ABSTRACT
Carbon monoxide is a ubiquitous molecule in organometallic chemistry and an
important feedstock in multiple catalytic processes both at the laboratory and industrial
levels. Palladium-catalyzed carbonylation reactions of alkenes/alkynes, aromatic halides
with different nucleophiles have undergone rapid development since the pioneering work
of Reppe and Heck, such that nowadays plethora of palladium catalysts and various
synthetic protocols are available for the synthesis of aliphatic and aromatic carboxylic
acids as well as their derivatives.
The carboxylic acid and its derivatives like amides, esters, thioamides etc. and
ketones prepared in this way are important intermediates in the manufacture of dyes,
pharmaceuticals, agrochemicals, and other industrial products. The term carbonylation
covers a large number of closely related reactions that all have in common that carbon
monoxide is incorporated into a substrate by the addition of CO to an aryl-, benzyl- or
vinylpalladium complex in presence of suitable nucleophiles.
Various carbonylation reactions like alkoxycarbonylation, phenoxycarbonylation,
aminocarbonylation, thiocarbonylation, carbonylative Suzuki coupling reaction,
carbonylative Sonogashira coupling reaction etc. have been explored using palladium as a
catalyst of choice.
Palladium along with variety of ligands has been widely employed as homogeneous
catalysts to affect carbonylation reactions. The scope of carbonylation reactions is also
extended for the synthesis of pharmaceuticals and their important intermediates using
carbonylation as the key step using homogeneous catalysis, which reveals that complex
synthetic processes can be accomplished under carbonylation conditions.
*
Corresponding author: Tel.: +91 22 33612601; fax: +91 22 33611020, Email address:
bhalchandra_bhnaage@yahoo.com, bm.bhanage@ictmumbai.edu.in.
206 Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage
Herein, we summarize the recent developments in homogeneous catalysts and

selected organic applications in this area.
INTRODUCTION
The development of environmentally benign and efficient synthetic methods continues to
be a central goal of current research in chemistry. In this regard, catalysis and organometallic
chemistry are key techniques for achieving these objectives and for contributing to a
“greener” chemistry in the future. Among the different catalytic reactions, the refinement of
readily available feedstock to more-functionalized products is of particular importance. Prime
examples for such transformations are carbonylation processes, which make use of carbon
monoxide currently the most important C1 building block. Hence, carbonylation represents
industrial core technologies for converting various bulk chemicals into a diverse set of useful
products of our daily life. For example, the conversion of olefins, the basic raw materials for
the chemical industry, by carbonylation gives access to more valuable products such as
aldehydes, alcohols and carboxylic acid derivatives.
The term carbonylation was coined by W. Reppe during the thirties and is generally used
to refer to those reactions in which CO alone or CO combined with other compounds
(especially nucleophiles with mobile H-atoms) are introduced into particular substrates
(Saturated or unsaturated). Carbonylation reactions rank among the most useful
transformations homogeneously catalyzed by transition metal complexes, forming the basis
for industrial and laboratory processes currently in practice [1-4]. Some of the initial scientific
discoveries in this field gradually evolved into large-scale commercial carbonylation
processes. Noteworthy among the commercial carbonylation processes are the ‘oxo’ process
(olefin hydroformylation) [5-7], the Reppe process (hydroxycarbonylation of acetylene to
acrylic acid) and Monsanto process (carbonylation of methanol to acetic acid) [8] etc. These
processes are employed worldwide to prepare millions of tones of commodity chemicals each
year.
Transition metal-catalyzed carbonylation of aryl halides in the presence of nucleophiles is
an important methodology for the preparation of aromatic carbonyl compounds which
includes ketones, amides, esters, acids and their derivatives [1-4]. The term carbonylation
covers a large number of closely related reactions that all have in common that carbon
monoxide is incorporated into a substrate by the addition of CO to an aryl-, benzyl- or
vinylpalladium complex in the presence of various nucleophiles (Scheme 1). In general,
aromatic halides are treated with an appropriate nucleophile in a carbon monoxide
atmosphere in the presence of a catalytic amount of a palladium complex, whereby, the
leaving group X is formally replaced by the nucleophile with incorporation of carbon
monoxide molecule. Typically, the reactions require a stoichiometric amount of base to
regenerate the catalyst.
In general, aromatic halides are treated with an appropriate nucleophile in a carbon
monoxide atmosphere in the presence of a catalytic amount of a palladium complex, whereby,
the leaving group X is formally replaced by the nucleophile with incorporation of carbon
monoxide molecule (Figure 1). Which of these products is obtained depends on the
nucleophile: water (hydroxycarbonylation), alcohols (alkoxycarbonylation), amines
(aminocarbonylation), alkyne (carbonylative Sonogashira), boronic acid (carbonylative
Homogeneous Catalysis in Carbonylative Coupling Reactions 207
Suzuki) etc. can be used. A variety of carbonylation products can be prepared from the same
aromatic substrate simply by changing the nucleophile, an advantage with respect to
biologically active compound libraries.
O
X
Palladium Nu
R + CO + Nu H R
Base
X = Cl, Br, I, OTf, N2-

Nu = OH, OR1, NR2R3 .......
Scheme 1. Pd-catalyzed carbonylation of aryl halides.
Nowadays, the use of carbon monoxide as a carbonyl source for aldehydes, ketones,
carboxylic acids and their derivatives in various transition metal-catalyzed reactions has
become probably the most widespread methodology for homogeneous catalytic reactions.
O O
R NRR'
R OH R OR
R-NHR'
R-
R-X
X
X
R-
H2
H
O
O
R-
O O
R-X R-X
R CO
R R R-SH
R SR
'
HR
R-
N
R-
X
R-
B
R-X
(O
H
)2
O O
RSnBu3
R'RN NRR' R R
O
R R
Figure 1. Pd-catalyzed carbonylation reactions.

The suggested mechanism for carbonylation reactions of aryl halide is shown in Figure 2.
The key steps in the mechanism of carbonylation reactions are, i) oxidative addition of aryl
halide to palladium to form aryl palladium halide complex; ii) insertion of carbon monoxide
into aryl palladium halide complex to form acyl palladium halide intermediate; iii) reductive
elimination to yield the product.
Initially there is oxidative addition of aryl halide to palladium which forms aryl
palladium halide complex (intermediate II). Coordination and migratory insertion of CO then
forms acyl palladium halide complex (intermediate III). The intermediate III is then attacked
by nucleophile and undergo reductive elimination to give carbonylated product. In the
catalytic cycle base plays a crucial role to generate a active palladium species which then
continues the catalytic cycle.
L
CO
Oxidative addition R Pd I
CO insertion
II
L
RI
L
PdLn R C Pd I
I
O L
Base
HI NuH III
L
Reductive elimination
H Pd I
R C Nu
L
O
Figure 2. General mechanism for Pd-catalyzed carbonylation of aryl halide.
Among the various carbonylation reactions, carbonylative coupling reactions has gained
considerable attention in recent years and several catalytic systems has been developed to
affect theses transformations. It has been observed that mostly homogeneous transition metal
catalysts are reported for carbonylative coupling reactions as they provide product in higher
yield at ambient conditions. Some of important contributions in this area are summarized
below.
CARBONYLATIVE SUZUKI COUPLING REACTION

Diarylketones constitute an interesting and versatile structural motif which is frequently
present in natural products (e.g. Cotoin, Papaveraldine), in non-steroidal anti-inflammatory
drugs (e.g. Suprofen, Ketoprofen) and occurs in UV screens (e.g. Sulisobenzone,

Oxybenzone) (Figure 3). Typically, diaryl-ketones are prepared by Friedel–Crafts acylation of
ortho/para-directing arenes with acyl halides [9]. Unfortunately, this reaction requires
overstoichiometric amounts of Lewis acid and the regioselectivity is often limited to the para-
position. Other synthetic strategies use cross-coupling reactions of benzoic halides with
organotin compounds [10-12], palladium-catalyzed coupling of boronic acids with carboxylic
anhydride [13] or nickel-catalyzed coupling reactions of aryl iodides with aromatic aldehydes
[14]. An especially versatile approach for the synthesis of diarylketones [15] is the transition-
metal-catalyzed three-component cross-coupling of Aryl-X (X = Br, I, OTf, N2+) derivatives,
carbon monoxide and aryl metal reagents. However, the coupling reaction of
organoaluminium [16] or organosilane [17] compounds with electron-poor aryl halides is
severely limited due to the formation of biaryl side products. Here, electron-withdrawing
groups on the aryl ring accelerate the rate of transmetallation to form the Ar–Pd–Ar
intermediate and hinder the insertion of carbon monoxide into the Ar–Pd–X species.
Palladium catalyzed carbonylative Suzuki coupling reaction is one of the most promising
method for direct synthesis of biaryl ketones from carbon monoxide, aryl halide and aryl
boronic acid.
O
N OMe O OH O OH
OMe
OMe OMe
OMe SO3H
OMe
Papaveraldine Sulisobenzone Oxybenzone
O OH O O
COOH
HO OMe S
COOH
Cotoin Suprofen Ketoprofen
Figure 3. Applications of Carbonylative Suzuki coupling reaction.
In 1993, Suzuki et al. introduced the coupling of aryl boronic acids with aryl iodides for
the synthesis of diarylketones (Suzuki carbonylation) (Scheme 2) [18]. In principle, these
reactions provide a versatile tool for diarylketones synthesis as boronic acids are generally
nontoxic and thermally, air and moisture stable. They used PdCl2(PPh3)2 as catalysts for this
transformation. Thoroughly they have investigated effect of base on selectivity of the
reaction, K2CO3 was found to give good yield of carbonylated products.
PdCl2(PPh3)2
Ar-B(OH)2 + CO + I-Ar ' Ar-CO-Ar '
Base
Scheme 2. Palladium catalyzed Suzuki carbonylation reaction.
Later on in 1998 they have developed PdCl2/dppf as a versatile catalyst for the same
reaction (Scheme 3) [19]. The catalyst was applicable for large variety of aryl electrophiles
such as aryl iodide, aryl bromide and aryl triflates. Furthermore they have proposed a possible
reaction mechanism.
O
PdCl2/dppf
B(OH)2 + CO + X C
Base
Y Z Y Z
Scheme 3. PdCl2/dppf catalyzed carbonylative Suzuki reaction.
Castanet et al. reported a simple and efficient method for the syntesis of α-pyridyl ketone
from chloropyridines using Pd(OAc)2/imidazolium salt as a catalyst (Scheme 4) [20]. Various
pyridine-chlorides were carbonylated with phenyl boronic acid to yield the desired product in
moderate to good yields (51-86 %).
Pd (OAc)2 - Imidazolium salt

X COPh
CO, PhB(OH)2, Base
N N
Scheme 4. Pd(OAc)2/imidazolium salt catalyzed carbonylative Suzuki reaction of halopyridines.
Further application of carbonylative Suzuki coupling reaction for the synthesis of

pyridylketones was explored by Castanet and group (Scheme 5) [21]. They developed a high
yielding protocol for the synthesis of α-pyridyl ketone using PdCl2 (PCy3)2 as a catalysts of
choice. The catalyst was applicable for various halopyridines providing moderate to excellent
yield of the desired products.
Palladium(II) acetate and N,N-bis-(2,6-diisopropylphenyl)dihydroimidazolium chloride
(2 mol%) was used to catalyze the carbonylative coupling of aryl diazonium tetrafluoroborate
salts and aryl boronic acids to form aryl ketones by Song et al. (Scheme 6) [22]. The reaction
was optimized with respect to various parameters such as time, temperature, CO pressure and
solvent. The catalyst system was applicable for variety of aryl diazonium tetrafluoroborate
salts and aryl boronic acids.
Scheme 5. PdCl2 (PCy3)2 catalyzed carbonylative Suzuki reaction of halopyridines.

-
i-Pr Cl i-Pr
- Pd (OAc)2 . N
Ph-N2+ BF4 O
I-Pr i-Pr
+
(OH)2B-Ph Ph Ph
CO
Scheme 6. Carbonylative coupling of aryl diazonium tetrafluoroborate salts and aryl boronic acids.
Carbonylative Suzuki coupling reaction 1-iodo-cyclohexene and phenylboronic acid (or

3-trifluoromethoxy-phenylboronic acid) was carried out using Pd(PPh3)4 complex by Kollar
and group (Scheme 7) [23]. The active catalyst Pd(0) is generated in-situ by the reaction of
Pd(OAc)2 and PPh3. The catalyst shows excellent activity for less reactive substrate i.e. 1-
iodo-cyclohexene providing good to excellent yield of the desired product, however,
substantial amount of byproduct was also forming in the reaction.
I
Pd (PPh 3 ) 4 Pd (PPh 3 )4
CO O
CO
O
OCF 3 B(OH) 2 B(OH) 2
OCF 3
Scheme 7. Carbonylative Suzuki coupling of 1-iodo-cyclohexene.
A new and efficient approach to the synthesis of α-ketosulfoxides by carbonylative

Suzuki coupling reaction between α-bromo sulfoxide, carbon monoxide and aromatic boronic
acids catalyzed by Pd(PPh3)4 has been developed by Asensio et al. (Scheme 8) [24]. The
carbonylative cross-coupling reaction is strongly favored over competing direct cross-
coupling and homo-coupling processes, except with boronic acids carrying strong electron-
withdrawing substituents. The reaction takes place under very mild conditions and with high
selectivity for a wide range of boronic acids. This method does not require an overpressure of
carbon monoxide or special ligands.
O O O
CO (1 atm), CsF
S Br + ArB(OH)2 S
Ph Pd (PPh3)4 Ph Ar
Scheme 8. Palladium-catalyzed three-component Suzuki cross-coupling reaction
Beller et al. reported Pd(OAc)2 /di-1-adamantyl-n-butylphosphine (cata CXium A) as

highly active catalyst in the three-component Suzuki carbonylation reaction (Scheme 9) [25].
The catalyst system was applicable for a broad range of aryl/heteroaryl bromides and aryl
boronic acids at low catalyst loadings. This reaction offers efficient access to various
biologically active compounds as shown by the two-step preparation of Suprofen.
O
Br B(OH)2
+ CO +
Pd (OAc)2 / L
MeO MeO
R
P
L =
Scheme 9. Pd/L catalyzed carbonylative Suzuki coupling reaction.

Bhanage and group reported the carbonylative Suzuki coupling reaction of aryl and
heteroaryl iodides with variety of arylboronic acids catalyzed by a well defined and stable
phosphine free palladium complex viz. palladium bis (2,2,6,6-tetramethyl-3,5-
heptanedionate) [Pd(TMHD)2] or Pd(OAc)2 as the catalyst (Scheme 10) [26]. The ease of
preparation of complex, high solubility in organic solvents, indefinite shelf life, stability
towards air and compatibility with various hindered and functionalized aryl/heteroaryl iodides
and arylboronic acids makes it an ideal complex for carbonylative Suzuki coupling reactions.
O B(OH)2 O
Pd(TMHD)2
Pd(TMHD)2/Pd(OAc)2
R R R
I X n
R1
+ I
n
R = CH3, OCH3, Br. R1 CO X
R1 = CH3, OCH3, No2, Br.
X = N, S.
n = 1 or 2
Scheme 10. Carbonylative Suzuki coupling reaction of aryl and heteroaryl iodide with phenylboronic
acid.
CARBONYLATIVE SONOGASHIRA COUPLING REACTION

The carbonylation reaction in which aryl halide reacts with carbon monoxide and alkyne
(as a nucleophile) to give alkynyl ketone as a product is known as carbonylative Sonogashira
coupling reaction. Depending upon the combination of aryl halide and alkyne, range of
alkynyl ketones can be produced.
Mori and co-worker reported palladium catalyzed carbonylative Sonogashira coupling of
terminal alkynes with aryl iodides under atmospheric pressure of carbon monoxide was
accomplished by using aqueous ammonia as a base in THF with or without use of CuI
(Scheme 11) [27]. The reaction was carried out at room temperature and furnishes 72% yield
of corresponding α,β-alkynyl ketone, while noncarbonylative coupling product is not
obtained.
O
X R
cat PdCl2(PPh3)2
+ R H + CO
aq NH3 (0.5 M)
room temp
Scheme 11. Palladium catalyzed carbonylative Sonogashira reactions.
Ryu et al. reported carbonylative three-component coupling reaction of aryl iodides with
terminal alkynes catalyzed by PdCl2(PPh3)2 using an ionic liquid, [BMim]PF6, as the reaction
medium, which resulted in good yields of α,β-acetylenic ketones (Scheme 12) [28]. They
have checked various ionic liquids, low-viscosity ionic liquid such as [BMim]NTf2 was not
suitable for this reaction, since the background Sonogashira coupling reaction, a competing
reaction, also proceeded.
O
X Ar
PdCl2(PPh3)2
+ R H + CO
[BMim] PF6
Scheme 12. PdCl2(PPh3)2/[BMim]PF6 catalyzed carbonylative Sonogashira reactions.
Ziolkowski and group shows PdCl2(P(OPh)3)2 mediated carbonylative coupling of

phenylacetylenes with aryl iodides in organic solvents and in ionic liquids (Scheme 13) [29].
With the aid of imidazolium ionic liquids, [BMim]PF6 or [MoCT]PF6 (BMim = 1-butyl-3-
methyl imidazolium cation, MoCT =1-methyl-3-octyl imidazolium cation) catalyst was
recycled and used for four consecutive catalytic cycles retaining its high activity. The
protocol was applicable for variety of substrates and moderate to good yields of desired
ketones were obtained.
O
X R
PdCl2 (P(OPh)3)2
+ R H
[BMim] PF6 or [MoCT] PF6
+ CO
Scheme 13. PdCl2(P(OPh)3)2 mediated carbonylative Sonogashira reactions.
Ryu et al. also showed application of multiphase microflow system for palladium
catalyzed carbonylative Sonogashira coupling reaction of aryl iodides with phenylacetylene
(Scheme 14) [30]. They have developed low pressure microflow system for palladium
catalyzed multiphase carbonylation reactions in an ionic liquid. The microflow system
resulted in superior selectivity and higher yields for carbonylative Sonogashira coupling
reactions of aryl iodides compared to the conventional batch system.
Me N N
Bu
Ph3P Pd Cl
Cl O
Ar-I + CO + Ph H Ph
[BMim]PF6, Et3N, 120 oC Ar
Scheme 14. Palladium catalyzed carbonylative Sonogashira reactions using multiphase microflow
system.
Chen and group have developed carbonylative coupling reaction of aryl iodides with
ferrocenylethyne catalyzed by PdCl2 using sodium dodecyl sulphonate (SDS) as surfactant
and water as solvent (Scheme 15) [31]. The reaction gave much better yields of aryl
ferrocenylethynyl ketones, which proceeded for 6 h at room temperature under a balloon
pressure of carbon monoxide using Et3N as base. The catalytic system was applicable for
large variety of aryl iodides providing moderate to excellent yield of the desired carbonyl
products.
O
C CH
C C C Ar
PdCl2/PPh3, Et3N
Fe
+ CO + Ar-I Fe
o
SDS, water, 25 C
Scheme 15. Palladium catalyzed carbonylative Sonogashira reactions of ferrocenylethyne.
Foldes et al. reported a two-step synthesis of ferrocenyl pyrazole and pyrimidine

derivatives based on carbonylative Sonogashira coupling of iodoferrocene with alkynes
(Scheme 16) [23]. New ferrocenyl 1, 3, 5-trisubstituted pyrazoles and 2,4,6-trisubstituted
pyrimidines were obtained by the addition-cyclocondensation reaction of the α, β-alkynyl
ketones with hydrazines and guanidinium salts, respectively. The products were obtained with
moderate to excellent yields and were characterized with the aid of various spectroscopic
tools.
Ar
I
Palladium Cat.
Fe + CO + Ar CH
Fe O
Ar
Ar
N
Fe N N
Fe N
R'
NHR'
Scheme 16. Pd catalyzed carbonylative Sonogashira reactions of iodo ferrocene.

A selective one-pot synthesis of carbonyl-containing N-heterocyclic compounds has been

developed using a carbonylative Sonogashira/cyclisation sequence by Djakovitch et al.
(Scheme 17) [33]. In order to get either indoxyl or 4-quinolone products selectively, various
catalytic protocols such as CO pressure, temperature, catalyst identity, base and
substrate/catalyst ratio were studied. The origin of the selectivity toward the 5-or 6-membered
ring compounds was explained through the respective role of the various catalytic species
involved, whether they are organic or metallic. The non-cyclic common intermediate was
selectively prepared using [PdCl2(dppp)] as catalyst. By using a two-step multi-catalysis, i.e.
{[Pd]+HNEt2}, 4-quinolones were obtained, whereas, with a tandem catalysis, i.e.
{[Pd]/PR3}, indoxyls were synthesized.
O
I
[Pd], base, solvent
+ + CO or
NH2 N N
H H
NH2
Scheme 17. Preparation of heterocyclic scaffolds via Carbonylative Sonogashira/cyclisation path.
Bhanage et al. reported a facile protocol for carbonylative Sonogashira coupling reaction
of aliphatic and aromatic alkynes with iodoaryls using a preformed Cu(TMHD)2 complex
(Scheme 18) [34]. This is the first report in which a copper complex is used as a catalyst for
carbonylative Sonogashira coupling reaction instead of palladium catalyst. The protocol was
general in nature applicable for carbonylative Sonogashira coupling reaction of wide variety
of aryl iodides with aromatic/aliphatic alkynes such as phenylacetylene, 1-hexyne and 1-
octyne etc.
O
I
CO
R H +
R
Cu [TMHD]2
Scheme 18. Cu[TMHD]2 catalyzed carbonylative Sonogashira coupling reaction.
AMINOCARBONYLATION REACTIONS
Among the carbonylative coupling reactions aminocarbonylation reactions are widely
explored because of appearance of amide functionality in various important compounds.
Transition-metal catalyzed three-component cross-coupling reaction between amine, carbon

monoxide and organic halides is now considered as a useful tool for the amide/anilide
synthesis (Aminocarbonylation). Heck et al. reported palladium catalyzed selective and useful
method for direct synthesis of amides via coupling of aryl, heterocyclic and alkenyl halides
with primary/secondary amines in presence of carbon monoxide [35-36]. Advantages of this
method include the broad availability of substrates and the high tolerance of palladium
catalysts against a variety of functional groups. Therefore, this route has become a useful tool
for the preparation of substituted amides, since those amides which are hardly available in
conventional synthetic methods can be synthesized from easily available starting materials.
Me
Cl
N
H Me
N N N
O
N C N
NH N
HN H
O N H2N
N O Cl
Procainamide
Imatinib (Gleevec) Boscalid
O O O
O C
N Ph NHPr
H
HO
N NH2 N
Cl
CJ-15,161, Pfizer
F
k-Opioid receptor antagonist
Mosapride
Figure 4. Examples of carbonyl product in pharmaceutical and material research.
Amides/anilides are attractive targets in chemical synthesis because of their wide utility
and occurrence in a number of interesting molecules. They have been found in biologically
important natural products, pharmaceuticals and agrochemicals. Amides are widely used as
an antiepileptic drug, anticonvulsants [37-38]. They are also used extensively in the polymer
chemistry [39-41].
Whittall and group explored Bedford-type palladacycle complex in combination with
dppf for the alkoxycarbonylation reactions (Scheme 19) [42]. They also extend the
application of this complex for the aminocarbonylation reaction. This palladium complex
acted as highly active catalyst for both the reactions showing compatibility with wide variety
of substrates.
Beller et al. demonstrated the aminocarbonylation of unprotected indoles with different N
and O-nucleophiles using Pd/dppf as a catalyst (Scheme 20) [43]. Various indole carboxylic
acid derivatives are accessible in excellent yield. For example, aminocarbonylation of 4-,5-,6,
or 7-bromoindole with arylethylpiperazines provides a direct one-step synthesis for CNS
active amphetamine derivatives. This is the first example for the carbonylation of unprotected
bromoindoles with various nucleophiles involving cyclic and acyclic amines, alcohols, and
Gee et al. had shown the application of microfluidic device for the rapid synthesis of amides
via aminocarbonylation reactions (Scheme 21) [44]. They showed the application of
microstructured device for first time to perform a gas–liquid carbonylation reaction. The
yields were moderate to good in very short period of time.
H
N
MeO MeO
O O
N +
OMe O N
Pd [1] / dppf,
CO
Br MeO
MeOH
O
OMe
Scheme 19. Palladacycle catalyzed carbonylation reactions.
Kollar et al. reported aminocarbonylation of 2-iodoaniline and derivatives using

Pd(OAc)2/PPh3 as a catalytic system. 2-Iodoaniline derivatives were used as bifunctional
substrates in palladium-catalysed carbonylation (Scheme 22) [45]. Depending on the
substituents, two types of compounds were synthesised: having methyl or hydrogen in 4-
position 2-aryl-benzo[1,3]oxazin-4-one derivatives have been formed, chloro, bromo, cyano
or nitro groups in the same position resulted in the formation of dibenzo[1,5]-diazocine-6,12-
dione derivatives. In the presence of various primary and secondary amines (t-butylamine,
amino acid methyl esters) as N-nucleophiles 2-ketocarboxamides were obtained as major
products in aminocarbonylation reaction with double carbon monoxide insertion.
NH
O
N
Ar
N
R
N
Ar N
H
R
Pd(PhCN)2Cl2
Br dppf, NEt3, CO
N O
H
Nu
NuH (RNH2, N
R2NH, ROH, H2O) H
Scheme 20. Pd/dppf catalyzed aminocarbonylation of bromoindoles.

X O
CO
NH2 N
+
H
R Pd-phosphine
catalyst R
Scheme 21. Pd/phosphine catalyzed aminocarbonylation reaction.
R
NH2
O
CO I CO NH
N R
Pd (OAc)2 / PPh3 Pd (OAc)2 / PPh3
O NH2
R HN R
R
O O
R = H, CH3, Cl, Br, CN, NO2 etc.
Scheme 22. Aminocarbonylation of 2-iodo aniline.
An efficient Pd(OAc)2/PPh3 catalyzed protocol for the aminocarbonylation of heteroaryl

iodides was reported Kollar and group (Scheme 23) [46]. Various primary and secondary
amines, including amino acid methyl esters, were used as nucleophiles in palladium-catalysed
aminocarbonylation of 2-iodopyridine, 3-iodopyridine and iodopyrazine. The reaction works
well with electron-rich and electron-poor substrates on nucleophile.
CO, HNRR' O
NRR' +
N I Pd(OAc)2 / PPh3 N N NRR'
O O
O O
I CO, HNRR'' NRR''
NRR''
+
O
N Pd(OAc)2 / PPh3 N N
Scheme 23. Pd(OAc)2/PPh3 catalyzed aminocarbonylation of heteroaryl iodides.
The application of aminocarbonylation for the synthesis of novel N-acyl phosphonates

with unprecedented structure was carried out by Kollar and group under mild and
homogeneous reaction conditions (Scheme 24) [47]. The palladium-catalyzed
aminocarbonylation of iodoalkenes (1-iodo-cyclohexene, 1-iodo-4-tert-butyl-cyclohexene, 1-
iodo-2-methyl-cyclohexene and α-iodostyrene) with diethyl α-aminobenzyl-phosphonate as
N-nucleophile resulted in the exclusive formation of carboxamides. The same reaction with
iodoaromatics (iodobenzene, 2-iodothiophene) provided the corresponding carboxamide in
high yields and some 2-keto-carboxamides as side products due to single and double carbon
monoxide insertion, respectively. The highly selective formation of carboxamides to
ketocarboxamides can be explained by favored single carbon monoxide insertion relative to
double CO insertion. The reaction tolerates structural variation of the iodo-substrate. The high
chemoselectivity and the easy work-up of the reaction mixtures make these reactions of
synthetic importance.
H
I H 2N P (O) (OEt)2 H H
O N
CO
+ P (O) (OEt)2
Pd (OAc)2 /PPh3
Scheme 24. Aminocarbonylation of α-aminobenzyl-phosphonate.
Further, aminocarbonylation of 1,8-diiodo-naphthalene with various primary and

secondary amines in the presence of palladium(0) complexes formed in situ from
palladium(II) acetate and triphenylphosphine was reported by Kollar and co-workers (Scheme
25) [48]. In the case of primary amines, depending on the amine to substrate ratio, two types
of products have been obtained in highly chemoselective mode: dicarboxamides and N-
substituted imides have been formed at high and low amine to substrate ratio, respectively.
The reaction tolerates the ester functionality, so that amino acid esters could serve as N-
nucleophiles and in this way, naphthalimides possessing stereogenic centre in the N-
substituent could be synthesised. The high chemoselectivity, the easy work-up of the reaction
mixtures, as well as the high functional group tolerance at the N-alkyl substituent and at the
aryl moieties, make these reactions of synthetic importance.
CO, H2NR
Pd (OAc)2 / PPh3
I I O N O
R
Scheme 25. Aminocarbonylation of 1,8-di-iodo-naphthalene.
A method for the aminocarbonylation of aryl bromide using xantphos as a ligand has
been reported recently by Buchwald and group (Scheme 26) [49]. The method is effective for
the direct synthesis of Weinreb amides, 1° and 2° benzamides and methyl esters from the
corresponding aryl bromides at atmospheric pressure of CO. The catalytic system was
applicable for variety of substrates providing good to excellent yield of desired carbonylated
products. In addition, a putative catalytic intermediate, (Xantphos)Pd(Br)benzoyl, was
synthesized, and an X-ray crystal structure was also showed. This crystal structure revealed
that this species possesses, in contrast to the majority of Pd-aryl complexes ligated by
Xantphos, a cis-coordinated palladium center.
O
Br
NucH, 1atm CO Nuc
R R
2-3 % Pd(OAc)2
2-6 % Xantphos
NucH = HN(OMe)Me, HNR2, MeOH
Scheme 26. Pd(OAc)2 /Xantphos catalyzed aminocarbonylation reaction.
Bhanage and co-workers reported the facile protocol for aminocarbonylation of aryl
iodides with aromatic/aliphatic amines catalyzed by phosphine-free palladium catalysts in
environmentally benign water as a solvent (Scheme 27) [50]. Excellent yields of desired
amides were obtained by using only 0.5 mol% of the catalyst under optimized reaction
conditions. The protocol is applicable for carbonylative coupling reactions of various electron
rich, electron deficient and sterically hindered aryl iodides with different amines affording
excellent yield of desired products.
R2 CO, Pd (OAc)2 O
R3
X + N
H Et3N, Water, 8 h NR2R3
R R
R = H, CH3, OCH3, NO2 R2/R3 = H, alkyl or aryl
Scheme 27. Pd(OAc)2 catalyzed aminocarbonylation reactions.
Pd (OAc)2 / PPh3 N O
N NaBH4 NH
Br Br
CO, K2CO3
LiAlH4
Scheme 28. Synthesis of protoberberine alkaloid using carbonylation reaction.

Orito et al. described preparation of protoberberine alkaloids which involves

carbonylation as one of the major step during synthesis (Scheme 28) [51].
Dihydroisoquinolines, the Bischler–Napieralski cyclization products reduced to
corresponding 1-(20-bromo-30, 40-dialkoxybenzyl)- tetrahydroisoquinolines using NaBH4 as
a reagent of choice. Carbonylation of 1-(20-bromo-30, 40-dialkoxybenzyl)-
tetrahydroisoquinolines by treatment with CO (1 atm) in the presence of Pd(OAc)2, PPh3 and
excess K2CO3 in boiling toluene gives 8-oxoberbines in good yields. Further, by treating with
excess LiAlH4, these lactams were converted almost quantitatively into protoberberine
alkaloids.
ALKOXYCARBONYLATION AND HYDROXYCARBONYLATION

REACTIONS
The carbonylation reaction in which aryl halide reacts with carbon monoxide and
phenol/alcohol (nucleophile) to give esters as a product is called as alkoxycarbonylation
reaction. Depending upon the phenol/alcohol employed one can get variety of aromatic or
aliphatic esters.
CO
Cl
P P COOR
ROH
R' Pd(OAc)2 R'
Scheme 29. Alkoxycarbonylation of aryl chlorides
1.2 equiv PhOH O

Cl 2 mol % Pd (OAc)2
4 mol % dcpp 2HBF4 OPh
R R
1.5 equiv K2CO3, CO (1 atm)
4Ao MS, DMF or DMSO,
100-120 oC, 6-24 h
Scheme 30. Pd(dcpp)2.HBF4 catalyzed alkoxycarbonylation reaction.
Bessard et al. reported a facile protocol for the alkoxycarbonylation of aryl chlorides
using palladium acetate in combination with phosphine containing ligands. They have shown
the coupling of different aryl chlorides with variety of aliphatic alcohols which provides
product in moderate to good yields (Scheme 29) [52].
Buchwald et al. reported carbonylation of aryl chlorides at ambient CO pressure using

Pd(dcpp)2.HBF4 as a efficient catalyst (Scheme 30) [53]. The catalyst was successfully used
for aryl and heteroaryl chlorides in combination with variety of a aliphatic and aromatic
alcohols. The catalyst is further employed for the synthesis of various acid derivatives via
carbonylation reactions.
Lei et al. demonstrated palladium-catalyzed alkoxycarbonylation of aryl iodides with a
thiourea-oxazoline type ligand under mild conditions (Scheme 31) [54]. Various functional
groups were tolerated and the yields were from moderate to excellent.
I COOEt
PdCl2(CH3CN)2, A
N N
Base, EtOH,
R CO(Ballon), 70 oC R S O
N
Scheme 31. Palladium/thiourea-oxazoline catalyzed alkoxycarbonylation reaction.
Bhanage et al. reported an efficient protocol for the alkoxycarbonylation reaction of aryl
iodide with alchohol and phenol as a nucleophile (Scheme 32) [55]. They employed
Pd(TMHD)2 as a phosphine-free homogeneous catalysts. The catalyst systems were
optimized with respect to various parameters and enabled carbonylation of electron-rich,
electron-deficient and sterically hindered aryl iodides, with different types of phenols and
alcohols affording excellent yields of the desired products.
O
I
Pd (TMHD)2 Nu
R R
CO, H-Nu.
Scheme 32. Pd(TMHD)2 catalyzed alkoxycarbonylation reaction.
The palladium-catalyzed carbonylation of aryl halide with carbon monoxide and water is
referred to as hydroxycarbonylation reaction. It allows the straightforward and atom-efficient
preparation of aromatic carboxylic acids. Depending upon the aryl halide used variety of
aromatic acids can be obtained.
Buchwald et al. demonstrated a mild, functional group tolerant method of the preparation
of phenyl acids and esters from aryl chlorides via palladium-catalyzed carbonylation reactions
using atmospheric pressure of carbon monoxide (Scheme 33) [53]. They employed Pd(OAc)2/
dcpp.2HBF4 as a catalyst for these conversions. The system is applicable for the synthesis of
variety of aryl and hetero aryl acid derivatives at low CO pressure.
2 equiv H2O O
Cl 2 mol % Pd (OAc)2
4 mol % dcpp 2HBF4 OH
R R
1.5 equiv K2CO3, CO (1 atm)
DMSO, 100-120 oC, 15 h
Scheme 33. Hydroxycarbonylation of aryl chlorides.
MISCELLANEOUS REACTIONS
Alper et al. reported carbonylation of acid chlorides with o-iodoanilines to produced-
substituted-4H-3,1-benzoxazin-4-ones in good to excellent yields (Scheme 34) [56-57]. The
reaction works well in the absence of phosphine containing ligands. The reaction is believed
to proceed via in situ amide formation from o-iodoaniline and acid chloride, followed by
oxidative addition to Pd(0), CO insertion, and intramolecular cyclization. The protocol was
applicable for variety of substrates providing good to excellent yield of desired heterocycles.
O
R I O Pd(OAc)2 R
O
+
NH2 Cl R
CO N R
Scheme 34. Palladium catalyzed carbonylation of acid chlorides with o-iodoanilines.

R
I R
Pd (OAc)2, Pyridine
+ R R + CO
OH n-Bu4NCl, DMF
O O
R
I R
Pd (OAc)2, Pyridine
+ R R + CO
n-Bu4NCl, DMF
NHCOOEt N O
Hydrolysis H
Scheme 35. Synthesis of coumarins and 2-quinolones using carbonylation reaction.
Starting from o-iodophenols or N-substituted o-iodoanilines and internal alkynes, Larock

and coworkers described several annulation processes involving heteronucleophilic attack on
the acylpalladium intermediate generated through intermolecular insertion of the internal
alkyne into s-aryl palladium complex followed by CO insertion for the synthesis of
heterocyclic compounds. These annulation processes represents the first examples of
intermolecular insertion of an alkyne on a s-aryl palladium complex occurring in preference
to CO insertion and allow the exclusive formation of coumarins and 2-quinolones (Scheme
35) [58-60]. Under optimized settings coumarins and 2-quinolones were obtained in moderate
to good yields. The selected reaction conditions utilize Pd(OAc)2, 2 equiv. of pyridine and n-
Bu4NCl, under CO (1 atm) in DMF at 100–120 °C.
Synthesis of 3-Substituted-3,4-dihydro-2H-1,3-benzothiazin-2-ones via palladium-
catalyzed carbonylation of 2-substituted-2,3-dihydro-1,2-benzisothiazoles was reported by
Alper et al. (Scheme 36) [61]. The reaction occurs at ambient pressure and temperature using
Pd(PPh3)4 as a highly active and regioselective catalyst. The carbonylative insertion process
occurs in good to excellent yields with total regioselectivity at the N-S bond of
benzisothiazole precursor and the reaction tolerates a number of substituents, including
primary and secondary alkyl groups and benzylic and naphthylmethyl functionalities.
S Pd (PPh3)4 S O
N R
CO (300 psi), 80 oC N
R
Pyridine
Scheme 36. Palladium catalyzed carbonylation of benzisothiazoles.
Orito et al. reported Pd(II)-catalyzed direct aromatic carbonylation, which proceeds with
remarkable site selectivity to afford a variety of five- or six-membered benzolactams from
secondary o-phenylalkylamines in a phosphine-free catalytic system using Pd(OAc)2 and
Cu(OAc)2 in an atmosphere of CO gas containing air (Scheme 37) [62]. The protocol was
used for synthesis of wide range of heterocycles by C-H activation of phenylalkylamines
without use of any expensive aryl halides under phosphine free conditions.
Pd (OAc)2
(CH2)n Cu (OAc)2 (CH2)n
NR NR
CO (1atm), toluene,
reflux
O
n = 1 or 2
Scheme 37. Synthesis of benzolactams via palladium catalyzed carbonylation.
Alper et al. demonstrates palladium-catalyzed cyclocarbonylation of o-iodoanilines with

imidoyl chlorides to produce quinazolin-4(3H)-ones in single step (Scheme 38) [63]. A wide
variety of substituted quinazolin-4(3H)-ones were prepared in 63-91% yields by the
palladium-catalyzed cyclocarbonylation of o-iodoanilines with imidoyl chlorides and carbon
monoxide. The reaction is believed to proceed via in situ formation of an amidine, followed
by oxidative addition, CO insertion and intramolecular cyclization to give the substituted
quinazolin-4(3H)-ones. The developed protocol was applicable for the synthesis of wide
range of substituted quinazolin-4(3H)-ones.
O
R I R1
N Pd(OAc)2 / PPh3 R R1
+ CO + N
NH2 Cl R2
N R2
Scheme 38. Cyclocarbonylation of o-iodoanilines with imidoyl chlorides.
Blaquiere et al. reported a novel strategy for the palladium-catalyzed multicomponent

synthesis of trisubstituted triazoles via carbonylation reactions (Scheme 39) [64]. This
approach features a wide scope, mild reaction temperatures and low carbon monoxide
pressure. Total yields range from 41% to 79%, or 80–94% per bond for the four bonds
created. As such, this method compares favourably with direct C-H arylation technology. The
protocol was applicable for the synthesis of wide variety of heterocycles and also underscored
for the synthesis of druglike and/or pharmaceutically relevant molecules from commercially
available materials.
Pd (OAc)2 / Xantphos OH
OH
Et3N, DMF HO
+ + CO N
4 - Hydrazino benzoic acid N
NH .HCl N
HOAc
HOOC
NH2
OH
Deferasirox
Scheme 39. Synthesis of deferasirox via Pd catalyzed multicomponent carbonylation reaction.
Recently, Beller et al. reported Carbonylative Heck coupling reactions of aryl and alkenyl
triflates with aromatic olefins (Scheme 40) [65]. This method represents a “missing link”
between the already established carbonylative Suzuki and Carbonylative Sonogashira
reactions. Starting from easily available aryl and alkenyl triflates the corresponding
unsaturated ketones are obtained good yields. The products obtained represent useful building
blocks for the synthesis of numerous biologically active compounds.
O
[(Cinnamyl) PdCl2]
ROTf + CO + dppp R
R'
R' toluene, NEt3
100 oC, 20 h
Scheme 40. Palladium catalyzed carbonylative Heck coupling reactions.

CONCLUSION
This review summarized the recent developments in the area of palladium-catalyzed
carbonylative coupling reactions of aryl halides and related starting materials in homogeneous
media. Since the original work of Heck and co-workers, various catalytic carbonylation
reactions have been developed over the past decades, and nowadays ranges of palladium
catalysts are available for these transformations. Thus an impressively diverse range of
efficient catalytic systems based on palladium have been developed during past years that
prove practical importance of carbonylative coupling reactions.
However, having a plethora of new synthetic catalytic methods for carbonylative
coupling reactions, the development of asymmetric catalysts for carbonylation reactions
needs to be explored. With regards to sustainability, a major challenge will be the
development of catalytic carbonylation reactions which do not use aryl halides as substrates,
but directly employ arenes. Again most of the carbonylation reactions are reported with
palladium catalysts however, these catalysts can be replaced by cheaper and easily available
metal catalysts such as Cu, Fe etc. Thus, carbonylation reactions using such catalysts are
indeed an area yet to discover.
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Chapter 8
SYNTHESIS, CHARACTERIZATION AND CATALYTIC

STUD OF OXOVANADIUM (IV) COMPLEXES
WITH TETRADENTATE SCHIFF BASES
A.P.A. Marques1,*, E.R. Dockal2, Ieda Lucia Viana Rosa1

and F.C. Skrobot3
1
LIEC – CMDMC, DQ, Universidade Federal de São Carlos, São Carlos, SP, Brasil
2
Laboratório de Sínteses Inorgânicas, Catálises e Cinética, DQ,
Universidade Federal de São Carlos, São Carlos, Brazil.
3
SENAI - Federação das Industrias do Estado do Paraná, Centro Cívico, Curitiba, Brazil.
ABSTRACT
The synthesis, characterization and catalytic study of Oxovanadium (IV)
complexes and yours precursors Schiff bases [N,N’-bis(salicylidene)-1,2-
phenylenediamine], [N,N’-bis(salicylidene)-1,3-phenylenediamine] and [N,N’-
bis(salicylidene)-1,3-xylylenediamine] are reported. The Schiff base ligands were
characterized by elemental analysis, melting points, Fourier Transformed Infra-red
spectroscopy, electronic spectroscopy and 1H and 13C Nuclear Magnetic Resonance
spectra. The oxovanadium (IV) complexes were characterized by elemental analysis,
melting points, Fourier Transformed Infra-red spectroscopy and electronic spectroscopy.
The oxidation catalytic of methyl phenyl sulfide with the complexes in solution and
heterogeneisated by means of supporting on alumina was studied. The catalytic reactions
were accompanied by gas chromatography; the catalytic products were characterized by
1
H Nuclear Magnetic Resonance and Fourier Transformed Infra-red spectroscopy. The
product of catalytic reaction, methyl phenyl sulfoxide, can be used as an intermediate in
the fabrication of pharmaceuticals. The oxovanadium (IV) complex from the Schiff base
[N,N’-bis(salicylidene)-1,3-xylylenediamine] presents the best catalytic activity in
homogeneous system probably due to its flexibility that favors the access of the substrate
to active center in the catalysis.
*
Corresponding author. Tel.: + 55 16 3351 8214; E-mail address: apamarques@liec.ufscar.br
234 A.P.A. Marques, E.R. Dockal, Ieda Lucia Viana Rosa et al.
Keywords: Oxovanadium (IV) complexes; Schiff base ligands; Synthesis; Catalytic

Reaction.
1. INTRODUCTION
Vanadium has aroused the interest of researchers since the discovery that various marine
species have this metal as an essential element [1]. Enzymes containing vanadium as an
essential element were isolated in the 1980’s. These enzymes are able to exercise the
activities of nitrogenase and bromoperoxydase [1]. Nowadays, a lot of papers deal with the
vanadium biochemistry [2]. Several vanadium compounds have recently been investigated in
animal model systems as treatment for diabetes [3, 4], and studies in clinical trials in human
beings with organic transition metal complex are been developed [5].
Oxovanadium (IV) complexes containing tetradentate Schiff bases have been the subject
of various studies [6-12]. Tetradentate Schiff base complexes of Oxovanadium (IV), VO2+,
are the subject of various studies in our laboratory [6, 8-10, 12]. The use of chiral
Oxovanadium (IV) complexes in the preparation of chyral sulfoxide for the medicine industry
has been widely studied [7]. One area of great interest also is the role of the vanadium species
in the oxygen-atom or electron transfer reactions [2, 8].
The development of new supported catalysts which combine the properties of
homogeneous catalysts with the benefits of heterogeneisation is of prime interest to the
chemical industry at present. The advantages are arising from ease of handling, recovery,
separation and recycling, coupled with the potential for automation which has become
recognized by more and more rank-and-file industrial and academic synthetic chemistry [13,
14] Heterogeneisation of homogeneous catalysis, through the complex supported in alumina,
not only solve the basic problem of catalyst separation, but also offer considerable economic
benefits if recycling and re-use would be possible [15, 16]. However, in some catalytic
reactions, the heterogeneisation of system can damage the reaction; the process of support of
the complex can become the active center more impeded and damage the reaction.
In this work, we describe the preparation and characterization of the Oxovanadium (IV)
complex of the tetradentate Schiff bases: N,N’-bis(salicylidene)-1,2-phenylenediamine, N,N’-
bis(salicylidene)-1,3-phenylenediamine and [N,N’-bis(salicylidene)-1,3-xylylenediamine],
named (salophen), (salmphen) and (salmxylen), respectively. The catalytic activity of the
[VO(salophen)] [VO(salmphen)] and [VO(salmxylen)] in the oxidation of the methyl phenyl
sulfide in acetonitrile, using tert-Butyl-Hydroperoxide as oxygen donnor in a homogeneous
system and supported on γ-alumina was studied.
2. EXPERIMENTAL
2.1 Materials
All solvents and reagents were of commercial grade unless otherwise stated and were
purchased from Merck and Aldrich. Methanol (MeOH), Ethanol (EtOH), acetonitrile (ACN),
dimethylsulfoxide (DMSO) and chlorophormio (CHCl3) were used as received.
Synthesis, Characterization and Catalytic Stud of Oxovanadium … 235
2.2 Synthesis of Schiff Base (L)
The Schiff bases were prepared by condensing of the diamine (1,2-phenylenediamine,

1,3-phenylenediamine and 1,3-xylylenediamine) with the salicylaldehyde in a 1:2 proportion,
in alcoholic solution (ethanol) [6-9]. The diamine (10 mmol) was added to a hot ethanol
solution, 50mL; the salicylaldehyde (20 mmols) was added in this mixture after 30 min. The
reactional system was stirred and warm at 60°C for 150min. After cooling slowly to room
temperature, the resulting precipitate was collected by filtration, washed with 20mL of
distilled water and 10mL of ethanol twice. The ligands were dried in vacuum at room
temperature.
2.3 Synthesis of [VIVO(Schiff Base)]
The complex [VO(salophen)], [VO(salmphen)] and [VO(salmxylen)] were prepared and

purified using an adaptation of the methods described previously [6-9]. A solution of
Oxovanadium (IV) sulfate (4.0mmol) in 20mL of distilled water was added to a hot ethanol
solution, 50mL, containing 4.0 mmol of the Schiff base ligand and sodium acetate trihydrate
(8.0 mmol). Although a precipitate formed almost immediately, the mixture was refluxed
with stirring for 3h, according to Scheme 1. After cooling slowly to room temperature, the
resulting precipitate was collected by filtration, washed with 20mL of distilled water and
10mL of methanol twice. The complex was purified by Soxhlet extraction using ethanol. The
purified complex was dried in vacuum at room temperature.
Schiff base + 2 NaOAc → (Schiff base)2- + 2 HOAc + 2 Na+
VO2+ + (Schiff base)2- → [VIVO(Schiff base)] ↓
Scheme 1.
2.4 Characterization of Schiff Base (L) and [VIVO(Schiff Base)] ([VO(L)])
Elemental analyses (C, N, H) were performed in an EA-1108 CHNS-O Fisons apparatus.

Fourier Transformed Infra-red (FTIR) spectra of the free ligand and the complex were
recorded in the 250-4000 cm-1 range as pressed discs (1% by weight in CsI) with a Bomem
Michelson 102 FTIR spectrophotometer. Electronic spectra were recorded in the 270-800 nm
range in CHCl3 using a MultiSpec-1501 Shimadzu instrument. The 1H and 13C Nuclear
Magnetic Resonance (NMR) spectra of the free ligand in DMSO were obtained using a
Bruker ARX 400 MHz 9.4T spectrometer.
2.5 Preparation of the Catalysts [VO(L)]-Alumina
[VO(L)] (0.1mmol) was added to a mixture of 0.250 g of support γ-alumina in

dichloromethano (25mL). This mixture was stirred and heated for 3 h. The solid was filtered
and washed thoroughly with distilled water till the washings were colorless. This exchange
procedure was repeated twice. The supported solid [VO(L)]-alumina obtained was dried at
100 °C overnight.
2.6. Catalysts Characterization
Scanning electron microscopies (SEM) were recorded on Stereoscan 440.

Thermogravimetric analysis (TGA) were carried out using the a TGA-951 thermogravimetric
unit coupled to a TGA-2100 thermal analyzer, both from TA Instruments, using sample mass
of ca. 7mg and a platinum sample holder under a N2 flow of 90mL min−1. In all experiments,
a 15 °C min−1 heating rate was used.
2.7. Oxidation of Methyl Phenyl Sulfide
Methyl phenyl sulfide (0.62mL, 5.3mmol) and 0.14g of the catalyst solids [VO(L)]-
alumina or the free complex [VO(L)] (0.169g, 0.34mmol) were added in ACN (25mL). To
this mixture was added the oxygen donor tert-Butyl-Hydroperoxide (t-BuOOH) (0.88 mL, 5.5
molar aq. solution, 5.3 mmol). Gas chromatographic analyses were carried out on a Shimadzu
chromatograph. Nitrogen was used as the carrier gas with a hydrogen flame ionization
detector. The DB-1 capillary column (length, 30 m; internal diameter, 0.25 mm) was packed
with 0.25 μm Megabore® film. The oxidation products were characterized by 1H RMN
(CHCl3) and IR (1% by weight in CsI, cm-1). The oxidation products yields were calculated
by the chromatograms area.
3. RESULTS AND DISCUSSION

The synthesis and characterization of the Schiff bases salophen and salmphen and yours
complexes were described previously elsewhere [10]. The Schiff bases salophen salmphen
and salmxylen and yours respectively complexes were stable in air, both in solution and in the
crystalline state. The yield of the purified complex and the ligand were listed in Table 1, the
yield variation between ligand and your respectively complex is probably due to differences
in the solubility of these compounds. The values obtained for elemental analysis were
consistent with the calculated ones to the molecular weight corresponding (Table 1) and the
graphic of the structures of the Oxovanadium (IV) complexes in Figure 1. The elemental
analyses indicate that the complex is monomeric specie formed by coordination of 1 mol of
the metal ion and 1 mol of the Schiff base ligand. The melt points of the ligands Schiff base
were minors that 100°C and of the complexes were higher 360°C and with short temperature
variation, the small interval of temperature is one indicative that the compounds are pure
(Table 1).
Table 1. Data of yield, melting point and elemental analysis of Oxovanadium (IV)
complexes and the salmxylen ligand.
Compound Formula(Mol. Weight) Anal. Found (Anal. Calc.) (%) Yield M. P.

(g mol-1) C H N (%) (°C)
[VO(salophen)] C20H14N2O3V(381.28) 63.3(63.3) 3.7(3.7) 7.3(7.3) 99 >360
[VO(salmphen)] C20H14N2O3V(381.28) 62.8(63.3) 3.8(3.7) 7.2(7.3) 84 >360
salmxylen C22H20N2O2(344.41) 74.2(76.7) 6.4(5.8) 8.0(8.1) 98 62
[VO(salmxylen)] C22H18N2O3V(409.33) 63.7(64.6) 4.4(4.4) 6.8(6.8) 86 >360
HC N O N CH
V
O O
(a)
HC N O N CH
V
O O
(b)
H2C CH2
HC N O N CH
V
O O
(c)
Figure 1. Structural representations of the complexes: [VO(salophen)] (a), [VO(salmphen)] (b) and
[VO(salmxylen)] (c).
Figure 2 presents the FTIR spectra in the 200-4000cm-1 range of (salmxylen) (A) and
[VO(salmxylen)] (B). The FTIR spectra of the free ligands and the complexes show various
bands in the 200-4000cm-1 region. Table 2 lists the most important and characteristic bands
of the FTIR spectra of the samples. The C=N stretching frequencies in the (salmxylen) occur
at 1634cm-1 as reported for similar ligands [8-10, 12, 17] The complex C=N stretching
frequency is expected to appear in lower frequencies when compared to the ligand. As it
noticed in Figure 2, the C=N stretching frequency is observed at 1617cm-1, indicating a
decrease in the bond order due to the coordinate bond of the metal with the azomethine
nitrogen lone pair [1, 18, 19]. The C-N stretching frequency has been reported in the 1340-
1020 cm-1 region [17, 20, 21]. In this case the band occurs near 1151cm-1 for the ligand and
around 1154cm-1 for the respective complex. The C-O stretching frequencies were observed
as strong bands at 1316 and 1116cm-1 for the ligand. For the complex they were noticed at
1312 and 1125cm-1. In similar compounds the C-O bands occur at 1390-1330 and 1260-
1000cm-1 [17, 20, 21].The characteristic V=O stretching frequency in the Oxovanadium (IV)
complexes appears as a medium-to-strong band at 980cm-1, Figure 2, i.e. within the 950-
1000cm-1 reported for similar Oxovanadium (IV) complexes [6, 8-10, 17, 18, 22, 23]. The
band in 611cm-1 is assigned to ν(V-N) and 450cm-1 is assigned to ν(V-O) as reported in
references [6, 8-10, 17, 18, 22, 23]. These bands were observed as new absorption peaks of
the complex and are not present in the spectrum of the free ligand.
Table 2. Relevant IR frequencies (cm-1) of the ligands and Oxovanadium (IV)

complexes.
Compound ν(C=N) ν(C-N) ν(C-O) ν(V=O) ν(V-N) ν(V-O)
salmxylen 1634 1151 1316; 1116 ----- ----- -----
[VO(salmxylen)] 1617 1154 1312; 1125 980 611 450
salophen 1616 1315 1366; 1193 ----- ----- -----
[VO(salophen)] 1607 1310 1380; 1197 985 542 389
salmphen 1622 1215 1279; 1200 ----- ----- -----
[VO(salmphen)] 1617 1217 1280; 1124 968 638 457
Table 3 lists the bands of the electronic spectra of the Schiff base ligands in solutions of
acetonitrile (ACN), trichloromethane (TCM) or dimethyl sulfoxide (DMSO), recorded in the
270-800nm region, theses spectra exhibit between four and two bands. The weak band, as a
shoulder, at 361nm is assigned to n→π* transition involving molecular orbital of the C=N
chromophore and the benzene ring [8, 9, 24-27]. The more important difference observed in
the electronic spectra of the Oxovanadium (IV) complexes, compared to the free ligands, is
the absence of the band assigned to pπ→d transition, around of 420nm. The isolated benzene
ring exhibits three characteristic absorptions around of 196-204, 210-244 and 255-278nm
assigned to π→π* type transitions [21]. The π→π* transition of the C=C and C=N
chromophores normally occur between 270 and 300nm [21]. The band around of 315-343nm
observed in the ligand is assigned to π→π* transition, which involves molecular orbitals
essentially localized on the C=N group and the benzene ring. In the complex it was observed
the same band at the same wavelength. The strong absorption band around of 278-316nm
observed only in the electronic spectra of the complex is assigned to π→π*of the benzene
ring [8-10, 21, 25-27].
[(sal)2(xilen)]
C=N
[VO(sal)2(xilen)]
V=O
C=N
4000 3000 2000 1000
Figure 2. FTIR spectra (200-4000 cm-1) of [(salmxylen)] and [VO(salmxylen)].
Table 3. Absorption data (nm) of electronic spectra of the Schiff base salophen,
salmphen and salmxylen in solutions.
Ligand Attributions Absorption Data λ(nm)

Solvent
ACN TCM DMSO
salmph n→π∗ (C=N) * * *
π→π∗ (C=N) 343 331 343
π→π∗ (C=C) 274 261 278
π→π∗ (C=C) 210 244 **
π→π∗ (C=C) 196 ** **
saloph n→π∗ (C=N) * 361 *
π→π∗ (C=N) 328 328 316
π→π∗ (C=C) 267 262 **
π→π∗ (C=C) 226 243 **
π→π∗ (C=C) 204 ** **
salmxy n→π∗ (C=N) * * *
π→π∗ (C=N) 315 317 316
π→π∗ (C=C) 255 257 **
π→π∗ (C=C) 215 ** **
π→π∗ (C=C) ** ** **
*band absent or hidden; **band out of area permitted for the solvent.
3 3
4 2 OH HO 2 4
5 1 1 5
6 6
7 N N 7
9
8 10 10 8
11 11
12
Figure 3. Numbering system of the carbon atoms for the RMN assignments.
The 1H and 13C NMR data of the Schiff base obtained from its spectra are given in
Table 4 and numbering system is presented in Figure 3. The 1H NMR spectrum of the Schiff
base in DMSO shows the peak characteristic of the OH as a singlet sign at 13.38ppm. The
singlets at 8.43ppm and 4.79ppm correspond to the CH=N and -CH2N, respectively. The free
ligand showed broad peaks between 7.45 and 6.87ppm due to hydrogen bonded phenolic
protons [8, 21]. The 13C NMR spectrum of the tetradentate Schiff base in DMSO shows the
peak concerned to CH=N at 165.8ppm. The sign of the carbon belonged to -CH2N group
appears at 63.1 ppm. The peaks between 117.0 and 161.0 ppm are assigned to the phenyl.
These values are in agreement with other similar Schiff base ligands [8, 27].
Table 4. 1H and 13C NMR data of the salmxylen ligands (chemical shifts in ppm).
Atom salmxylen
1 13
H NMR (ppm) C NMR (ppm)
C1 --- 118.8
C2 --- 161.0
C3H 7.30-6.9mc 117.0
C4H 7.30-6.9mc 132.4
C5H 7.30-6.9mc 118.6
C6H 7.30-6.9mc 127.1
C7H 8.43s 165.8
C8H 4.79s 63.1
C9H 7.45s 131.5
C10 --- 138.6
C11H 7.33d 129.0
C12H 6.87t 126.0
δOH 13.38s ---
s
, singlet; d, doublet; dd, doublet of doublets; t, triplet; mc, multiplet complex
Sy
ynthesis, Charracterization and
a Catalytic Stud
S of Oxovaanadium … 241
(a) (b)
Fiigure 4. SEM im
mages of [VO(ssalmxylen)]–aluumina (A) and alumina
a (B) - 100μm.
Figure 4 presents SEM images of [V VO(salmxylen))]–alumina (A A) and aluminna (B). The

SE EM image sh how the variaation in the surface of thee alumina afteer the adsorpttion of the
[VVO(salmxylenn)] and the diistribution hoomogeneous of o the compleex in the surfface of the
allumina.
Differentiaal thermal anaalysis has been used to chaaracterize the complex heyyerogenized
[228, 29]. Throu ugh this analyysis, it can be noticed that thhe alumina is thermal stablle material.
H
However, the expected looss of masss due to the organic liigand of thee catalysts
[VVO(samxylen))]-alumina was w practicallly impercepptible, probabbly due to the low
cooncentration ofo [VO(samxylen)] in this suupport.
Figure 5 prresents the prrogression of thet oxidation reactions of methyl
m phenyl sulfide in
thhe presence of o free [VO(L L)], [VO(L)]-alumina and pure γ-Alum mina, using t-B BuOOH as
oxxygen donor and a ACN as solvent.
s Tablee 5 presents thhe results of thhe catalytic oxidation of
m
methyl phenyl sulfide for the studied systtems. Figure 5 and Table 5 shows that thhe catalytic
syystems consisting of [VO(ssalophen)]-aluumina and γ-aalumina withoout the compleex, did not
prresent any acctivity on thee catalytic oxxidation of methyl
m phenyl sulfide. Hom mogeneous,
[VVO(salophen)]], [VO(salmpphen)] and [V VO(salmxylenn)], and heterrogenized Oxovanadium
(IIV) complexes, [VO(salmphen)]-aluminaa and [VO(salmxylen)]-aluumina, presentted activity
onn the catalyticc reaction. How wever, the hetterogenized syystem showed considerable conversion
onnly after 24 hours
h of reacttion to [VO(ssalmphen)]-aluumina and [V VO(salmxylen))]-alumina,
m
more longer thaat the homogeeneous systems.
After 5 hou urs of reactionn only 6 mol%% of the sulfidde was oxidizeed to sulfoxidde when the
[VVO(salmphen))]-alumina cattalyst was useed; while 69 mol% and 222 mol% of thee sulfoxide
w produced for [VO(salm
were mphen)] and [V VO(salophen)]] homogeneouus catalysts, reespectively.
The [VO(salmx xylen)] homogeneous catallysts not presented catalytiic activity in 5 hours, it
syystem presenteed an less incrrease in the suulfide oxidatioon after 24 houurs of reactionn (8 mol%)
annd at 48 houurs produced 15 mol% of sulfoxide. Thhe [VO(salmxxylen)]-aluminna system,
coompared withh [VO(salmxyylen)] homogeeneous system m, showed be more adequaate because
affter 24 and 488 hours of reacction this systtem produced 87 and 92 mool% of sulfoxiide, around
off ten times moore that the hoomogeneous syystem. Howevver, the heterogeneous systeems present
o day it wass observed an increase in
acctivity catalytiic only at reacctions times loonger. After one
thhe product yield,
y which values weree 73, 75, and a 87 mol% % for [VO(salophen)],
[VO(salmphen)] and [VO(salmxylen)]-alumina, respectively. These oxidation reactions were

monitored for one day when the conversion was stabilized at 95 mol% for [VO(salophen)],
100% for [VO(salmphen)] and 92 mol% for [VO(salmxylen)]-alumina. The results for
[VO(salmxylen)]-alumina system show a differentiate increase after this time (92 mol%),
compared to the 5 hours reaction (0 mol%). It was observed in [VO(salophen)] and
[VO(salmphen)] systems the formation of two products for the sulfide oxidation,
corresponding to 75 mol % of sulfoxide and 20 mol % of sulfone to [VO(salophen)] system
and 83 mol % of sulfoxide and 17 mol % of sulfone to [VO(salmphen)] system.
100 [VO(salophen)]-alum and γ−alum

[VO(salmphen)]-alum
[VO(salmxylen)]-alum
80 [VO(salophen)]
[VO(salmphen)]
[VO(salmxylen)]
Conversion (%)
60
40
20
0 50 100 150 200 250 300 1000 1500 2000 2500 3000
Time (min)
Figure 5- Accompaniment of the oxidation reactions of methyl phenyl sulfide in the presence of
[VO(salmphen)] (-{-), [VO(salmxylen)] (-V-), [VO(salophen)] (-U-), [VO(salmphen)]-alumina (-z-
), [VO(salmxylen)]-alumina (-T-), [VO(salophen)]-alumina and γ-alumina pure (-S-).
In first the 240 minutes (four hours) the [VO(salophen)] does not promote the oxidation
of the sulfide, whereas the catalytic [VO(salmphen)] system produced 42% of sulfoxide;
however at long time of reaction both had converted sulfide to sulfoxide and sulfone. This
characteristic suggests that the bridge in position 1,3 of [VO(salmphen)] becomes the active
center more unimpeded than the bridge in position 1,2 of [VO(salophen)], what it facilitates
the approach of the substrate to active center, consequently, the oxidation of this occurs more
easily. The occurrence of the formation of sulfoxide and sulfone in the systems
[VO(salophen)] and [VO(salmphen)] in solution it suggests that the active center possess high
degree of desprotection what it facilitates the approach of the substrate, and, in the system
[VO(salmxylen)] in solution the structure possess a distortion able to hinder the approach it
substrate to the active center, diminishing the formation of product.
It was observed that in the homogeneous catalytic system with intermediate structural
flexibility and in the heterogeneous systems that possess complexes with additional flexible
structures present better catalytic activity. These observations suggest that the alumina
support becomes the molecule most rigid and with the more impeded active center, being
thus, the capable complex of bigger distortion are what it possess betters conversions, in this
case [VO(salmxylen)]. In the homogeneous system the complex is free and its distortions can
turn the active center impeded, thus intervening with the catalytic reaction.
Table 5. Methyl phenyl sulfide conversion (mol%) in the [VO(L)], [VO(L)]-alumina

and pure γ-alumina, where L: salmxylen, salmphen or salophen.
Time Methyl phenyl sulfide conversion (mol%)
(min) [VO(salmxylen)] [VO(salmphen)] [VO(salophen)] Pure γ-
alumina
homog. heterog. homog. heterog. homog. heterog.
60 0 0 3 0 0 0 0
120 0 0 18 0 0 0 0
180 0 0 21 0 0 0 0
240 0 0 42 0 0 0 0
300 0 0 69 6 22 0 0
1440 8 87 75 12 73 0 0
7200 34 92 100 43 88 0 0
The products of oxidation of methyl phenyl sulfide were characterized by FTIR and 1H
NMR data. The sulfide is characterized by S-C stretching (νS-C) around 740cm-1. The S=O
(νS=O) and SO2 (νSO2) stretchings are characterized by the bands at 1089 and 1161cm-1,
respectively. The 1H NMR showed peaks near 2.48, 2.81 and 3.06ppm assigned to sulfide,
sulfoxide and sulfone, respectively. These data are in agreement with chromatographic data,
where the homogeneous systems present sulfoxide and sulfone as catalytic products only at
long times of reactions (more than 24 hours). Long reaction time favors the re-oxidation of
substrate, forming sulfone with sub-product. Because of this fact, it is suggested that long
time of reaction is not recommended to the oxidation of sulfide to sulfoxide, consequently,
the homogeneous catalysis is more efficient that the heterogeneous catalysis because
promotes the oxidation in less time reaction.
CONCLUSION
The results showed indicate that the synthesis of ligand and complex were efficient. The
catalytic study demonstrated that pure alumina and [VO(salophen)]-alumina were not good
catalysts in the oxidation of methyl phenyl sulfide. The catalysis results indicate a good
activity of the catalysts [VO(L)] and [VO(L)]-alumina for the oxidization of methyl phenyl
sulfide to sulfoxide, however, the superior time of reaction favors the re-oxidation of
substrate, forming sulfone with sub-product. The homogeneous system was the best system to
oxidation reaction of sulfide to sulfoxide, with good rate conversion. The [VO(salmphen)]
system, showed an increase in the substrate oxidation compared to the other ones in minors
time of reaction, probable because in [VO(salmphen)] system the catalytic active center is
less impeded, facilitating the oxidation of the methyl phenyl sulfide.
ACKNOWLEDGMENTS
Financial support from the Fundação de Amparo à Pesquisa do Estado de São Paulo
(FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and
Petrobras to cede the zeolite.
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[19] K. P. Callahan, P. J. Duran, Inorganic Chemistry 1980, 19, 3211.
[20] N. B. Colthup, L. H. Daly, S. E. Wiberley, Introduction to Infrared and Raman
Spectroscopy, Academic Press, Inc., San Diego, 1990.
[21] R. M. Silverstein, G. C. Bassler, T. C. Morril, Spectrometric Identification of Organic
Compounds, Wiley, New York, 1991.
[22] J. C. Pessoa, I. Tomaz, R. T. Henriques, Inorganic Chimica Acta 2003, 356, 121.
[23] A. El-Dissouky, A. K. Shehata, G. El-Mahdey, Polyhedron 1997, 16, 1247.
[24] J. R. Zamian, E. R. Dockal, G. Castellano, G. Oliva, Polyhedron 1995, 14, 2411.
[25] E. H. F. Brittain, Introdution to Molecular Spectroscopy: theory and Experiment.,
Academic Press, London,, 1970.
[26] B. Bosnich, Journal American Chemistry Society 1968, 90 627.
[27] R. C. Felício, E. T. G. Cavalheiro, E. R. Dockal, Polyhedron 2001, 20, 261.
[28] H. Diegruber, P. J. Plath, G. Schultz-Ekloff, 1984, 24, 115.
[29] S. P. Varkey, C. Ratnasamy, P. Ratnasamy, Journal Molecular Catalysis A: Chemstry
1998, 135, 295.
Editors: Andrew C. Poehler ©2011 Nova Science Publishers. Inc.
Chapter 9
UNIQUE DESIGN TOOLS FOR THE SYNTHESIS

AND DESIGN OF DENDRIMERS AS SUPPORTS
FOR RECOVERABLE CATALYSTS
AND REAGENTS AND THEIR APPLICATIONS
IN ASYMMETRIC SYNTHESIS
Ashraf A. El-Shehawy*
Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
Kafr El-Sheikh University, Kafr El-Sheikh, Egypt
ABSTRACT
The use of soluble supports leads to recyclable catalyst systems that do not suffer
from mass transfer limitations, and therefore they should lead to systems with activities
similar to their monomeric analogues. Catalysis seems to be a research area in which
promising applications for dendrimers may be developed. Indeed, dendritic catalysts are
nanosized, and as such they are, as biomolecules, easily isolable from homogeneous
reaction media by precipitation, filtration, ultrafiltration or ultracentrifugation. In
particular, dendrimers have recently attracted a lot of attention, since these well-defined
macromolecular structures enable the construction of precisely controlled catalyst
structures. This combination of features makes dendrimers suited to close the gap
between homo- and heterogeneous catalysis, or, in other words, dendrimers will combine
the advantages of homo- and heterogeneous catalysis. Dendrimers have a number of
potential applications, but the present chapter is specifically focus on summarizing the
major concepts for their properties as well as the most pronounced advances for their
applications as supports for recoverable catalysts and reagents in asymmetric synthesis.
* Department of Nanobio Materials and Electronics, School of Materials Science and Engineering, and Research
Institute for Solar & Sustainable Energies (RISE), Gwangju Institute of Science and Technology (GIST), 1
Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea (Tel.: +82 62 715 3463 & Fax: +82 62 9702304;
E-mail: elshehawy2@yahoo.com)
Department of Chemistry, Faculty of Science, Kafr El-Sheikh University, Kafr El-Sheikh 33516, Egypt (Tel.: +20
47 3215173 & Fax: +20 47 3215175)
248 Ashraf A. El-Shehawy
This chapter highlights some of the notable examples of the catalytic reactions using
supported dendritic catalytic systems in such reactions as hydrogenation,
hydroformylation, alkyation, epoxidation, dialkylzinc addition to aldehydes and imines,
Heck and other Pd-catalyzed C-C bond formation. The intriguing properties of
dendrimers in catalysis including activity, selectivity, stability, and recyclability will be
addressed. Further key issues in this chapter relate to the deviating properties of
dendrimers as compared to their linear macromolecular counterparts is considered.
Keywords: Dendrimers, hyperbranched polymers; dendritic catalysis; chiral dendrimers;

chiral polymers; asymmetric synthesis; asymmetric catalysis, recoverable catalysts and
reagents
1. INTRODUCTION
The development of well-defined catalysts that enable rapid and selective chemical
transformations and can be separated completely from the products is still a paramount
challenge.[1] The recent success of homogeneous catalysis is reflected in the number of
applications that is known today both in the laboratory and in the industrial practice, but so
far there is not a single solution to the catalyst-product separation problem. In fact, all “unit
operations” for separation, including distillation, liquid-liquid separation or extraction,
stripping, catalyst destruction, and crystallization, are being applied in industry. While several
methods are being applied commercially, the search for new approaches continues. A widely
studied approach to facilitate catalyst product separation is the attachment of homogeneous
catalysts to insoluble organic, inorganic, or hybrid supports.[1b,e,h,i,k,2] Catalysts supported
on highly cross-linked polymer beads generally suffer from diminished activity compared to
the homogeneous analogues, which is because of a reduced accessibility.[1h,2,3] The use of
soluble supports leads to recyclable catalyst systems that do not suffer from mass transfer
limitations, and therefore they should lead to systems with activities similar to their
monomeric analogues.[1a-c, d,f,g,j,k,m,4]
Dendrimers are a new class of polymeric materials. They are highly branched,
monodisperse macromolecules. Furthermore, the high degree of branching renders
entanglement of the polymers impossible, which results in low melt and solution viscosity.
The structure of these materials has a great impact on their physical and chemical
properties.[1a,k,l,5] As a result of their unique behavior, dendrimers are suitable for a wide
range of biomedical and industrial applications.[1a,c,d,f-h,k-n,4a,6] Indeed, dendrimers offer
a unique opportunity to combine the advantages of homogeneous and heterogeneous catalysis
yet keep the well-defined molecular features required for a fully detailed analysis of the
catalytic events. It is possible to tune the structure, size, shape, and solubility of dendrimers.
Many of the intriguing properties of dendrimers as well as their syntheses and possible
applications are discussed in excellent books and reviews that have been published by various
experts in the field.[1a-d,f-i, l-n, 4a,b, 5c,6a,c]
To give an answer to the question “what can dendrimers add to the field of catalysis?” we
have to take a closer look at the ideal catalyst. From a catalytic point of view the ideal catalyst
is highly active and selective under mild conditions, very stable and can be separated from the
product using a relatively simple process. Right from the start, the regular monodisperse
Unique Design Tools for the Synthesis and Design of Dendrimers … 249
structure and multiarm topology of dendrimers inspired chemists to propose dendrimers with
peripheral catalytic sites as soluble supported catalysts. In 1994, Tomalia and Dvornic
discussed the promising outlook of surface functionalized dendrimer catalysts.[7] Dendritic
catalysts are often proposed to fill the gap between homogeneous and heterogeneous
catalysts. However, keeping in mind that heterogeneous systems generally contain at least
1012 active sites per conglomerated particle, it is fair to state that the class of dendritic
catalysts, containing at most 1000 active sites, is closer to the monomeric homogeneous
systems. A better formulation is that functionalized dendrimers potentially can combine the
advantages of both homogeneous and heterogeneous catalytic systems. Dendrimers have
some unique properties because of their globular shape and the presence of internal cavities.
Their globular shape makes these systems more suitable for recycling than soluble polymer-
supported catalysts. The most important one is the possibility to encapsulate guest molecules
in the macromolecule interior.[1c,m, 4a, 6b,c,8]
In this chapter, we do not want to present a comprehensive or complete overview on the
reported dendrimers, but, instead, we highlighted the most interesting studies that contribute
to a better understanding the properties of dendrimers. Some of the notable examples on their
uses as supports for recoverable catalysts and reagents in asymmetric synthesis will be
discussed. The intriguing properties of dendrimers in catalysis including activity, selectivity,
stability, and recyclability will be addressed. Further key issues in this chapter relate to the
deviating properties of dendrimers as compared to their linear macromolecular counterparts.
We hope to show that dendrimers are a unique class of macromolecules with a bright future
ahead.
2. DENDRITIC STRUCTURES
In the first instance, dendritic catalysts were proposed to be easily recyclable
homogeneous catalysts. The question is, however, if they also can provide systems that are
either more active or selective or more stable than their homogeneous monomeric analogues?
This would yield systems with interesting novel catalytic properties providing an intrinsic
solution for the homogenous catalyst separation problem. These novel properties induced by
the dendritic framework depend on the location of the functional group within the structure.
One should distinguish periphery-functionalized (dendrimer or a dendritic wedge), core-
functionalized, and focal-point functionalized (dendritic wedge) systems (see Figure 1). A
combination of these conceptual approaches might lead to systems with different catalytic
centers, which are ideally suited for cascade reactions.
Periphery-functionalized dendrimers have their ligand systems, and thus the metal
complexes, at the surface of the dendrimer. The transition metals will be directly available for
the substrate, in contrast to core-functionalized systems, for example, in which the substrate
has to penetrate the dendrimer prior to reaction. This accessibility allows reaction rates that
are comparable with homogeneous systems. On the other hand, the periphery-functionalized
systems contain multiple reaction sites and ligands, which results in extremely high local
catalyst and ligand concentrations. Furthermore, if a reaction proceeds by a bimetallic
mechanism, the dendritic catalysts might show better performance than the monomeric
species.[9] On the other hand, several deactivation mechanisms operate by a bimetallic
mechanism, for example, ruthenium-catalyzed metathesis,[10] palladium-catalyzed reductive

coupling of benzene and chlorobenzene,[11] and reactions that involve radicals.[12]
Figure 1. Catalytically active transistion metal complexes can be attached to the periphery (a), at the
core (b), at the focal point of a wedge (c), and at the periphery of a wedgel.
In core- (and focal-point-) functionalized dendrimers, the catalyst could benefit especially
from the site isolation created by the dendritic environment. Site-isolation effects in
dendrimers can be beneficial for other functionalities.[13] For reactions that are deactivated
by excess ligand or in cases in which a bimetallic deactivation mechanism is operative, core-
functionalized systems can specifically prevent such deactivation pathway, whereas
periphery-functionalized systems might suffer from relative low activity. Core-functionalized
dendrimers may benefit from the local catalyst environment created by the dendrimer. Effects
of desolvation of the substrate during the penetration of the dendrimer might be of
importance, but very little is known about these effects. In nature, enzymes make use of these
effects when substrates enter the active site of such systems.
Another significant difference between core- and periphery-functionalized dendrimers is
the molecular weight per catalytic site. Much higher costs will be involved in the application
of core-functionalized systems and application can also be limited by the solubility of the
system (to dissolve 1 mmol of catalyst 20 gL-1 is required (MW 20 000 Da, 1 active site)
compared to 1 gL-1 (MW 20 000 Da, 20 active sites). On the other hand, for core-
functionalized systems the solubility of the dendritic catalyst can be tuned by changing the
end groups.
3. PURITY OF DENDRIMERS
Higher generation dendrimers reach molecular masses that in earlier days had not been
accessible through directed organic reactions, apart from through polymerization reactions,
which lead to products with a broad distribution of molecular masses (polydisperse).[14]
They are modelled on natural globular biomacromolecules that are able to perform certain
functions as a consequence of their defined three-dimensional formation through hydrogen
bonds. Hence, the three-dimensional structure of high-molecular compounds, such as
dendrimers, is of great interest, since the dendrimers differ from biological macromolecules,
such as proteins, in their three-dimensional covalently linked skeleton. According to an early

theoretical work on idealized structures,[15] it was postulated that dendrimers of lower
generations take a rather flat, ellipsoidal shape. Assuming that in divergently synthesized
dendrimers each branch is directed radially towards the outside and that the end groups lie on
the surface of an ellipsoid, the macromolecules transform into a more spherical shape from a
certain generation upwards (depending on the core molecule, branching multiplicity, and the
length of the branch segment). Simple calculations have shown that the area of an end group
on this ellipse becomes continually smaller with an increasing number of generations until a
critical branched state, the so-called “Starburst dense packing”, is reached and prevents any
further reaction.[16] Hence, the molecules are meant to be spherical constructions with a
dense exterior and a loose interior with channels and cavities. Experimental results, for
example, the inclusion of guest molecules and the viscosity, confirm this assumption. Thus,
dendrimer chemistry has become a part of supramolecular chemistry.
Generally, two conceptually different synthetic approaches for the construction of high
generation dendrimers exist: the divergent approach and the convergent approach. Both
approaches consist of a repetition of reaction steps, each repetition accounting for the creation
of an additional generation. The two methodologies have their own characteristics, and
therefore, the perfection of the final dendritic product is related to this synthetic approach. In
the divergent synthesis, the dendrimer is grown in a stepwise manner from a central core,
implying that numerous reactions have to be performed on a single molecule. Consequently,
every reaction has to be very selective to ensure the integrity of the final product. For
example, an average selectivity of 99.5% per reaction will, in the case of the synthesis of the
fifth generation poly(propylene imine) dendrimer (64 amine end groups; 248 reactions, see
Scheme 1), only result in 0.995248 = 29% of defect-free dendrimer.[17,18]
Since every new generation of divergently produced dendrimer can hardly be purified,
the presence of a small number of statistical defects cannot be avoided. Bearing this in mind,
the divergent synthesis can be seen as the macromolecular approach toward dendrimers: the
purity of the dendrimers is governed by statistics. The reality of statistical defect structures is
also recognized in the iterative synthesis of polypeptides or polynucleotides on a solid support
(the Merrifield synthesis),[19] so the knowledge gathered in this field should be considered
when the perfection of dendritic structures is discussed.
Scheme 1. The synthesis of poly(propyleneimine)dendrimers (reaction A and B) and alternative

unwanted reaction paths C and D. Path C illustrates “missed Michael additions (either by an incomplete
cynaoethylation or by a retro-Michael reaction). Paths C and D describe sefect reactions on going from
one amine generation to the next.
In the convergent approach, the difficulty of many reactions that have to be performed on
one molecule has been overcome by starting the synthesis of these dendrimers from the
periphery and ending it at the core. In this fashion, a constant and low number of reaction
sites are warranted in every reaction step throughout the synthesis. As a consequence, only a
small number of side products can be formed in each reaction, and therefore, every new
generation can be purified (although the purification of higher generation materials becomes
increasingly troublesome). Thus, convergently produced dendrimers, which can be seen as
dendrimers prepared in an “organic chemistry approach”, can be defect-free.
4. STRUCTURAL ANALYSIS OF DENDRIMERS

Dendrimers pertain both to the molecular chemistry world for their step by step
controlled syntheses, and to the polymer world because of their repetitive structure made of
monomers; thus they benefit from analytical techniques from both worlds. The
characterization of dendrimers is rather complex due to the size and symmetry in these
macromolecules. Caminade and Majoral et als have been surveyed the main analytical
techniques used for the characterization of the chemical composition, the morphology, the
shape, and the homogeneity of dendrimers.[18] This review included the use of NMR, IR,
Raman, UV–Visible, fluorescence, circular dichroism, X-ray diffraction, mass spectrometry,
SAXS, SANS, Laser Light Scattering, microscopy, SEC, EPR, electrochemistry,
electrophoresis, intrinsic viscosity, DSC, and dielectric spectroscopy in the characterization of
dendritic macromolecules. Various NMR techniques (1H, 13C, 15N, 31P), elemental analyses,
and chromatography techniques (HPLC, SEC) are widely used, but these techniques cannot
reveal small amounts of impurities in, especially, higher generation dendrimers.[18,20] A
progress in ESI (electrospray ionization) and MALDI (matrix-assisted laser desorption
ionization) mass spectrometry allows for an in-depth analysis of dendrimers. ESI-MS has
been used to identify the imperfections in both poly(propylene imine)[17b,20] and poly
amido amine (PAMAM) dendrimers.[21] Both of these dendrimer types are made via a
divergent synthesis and are very suitable for electrospray ionization due to their polar and
basic nature.
All generations of poly(propylene imine) dendrimers with either amine or nitrile end
groups have been analyzed with ESI-MS to quantitatively determine the importance of
various side reactions.[17b] In the approach followed, all possible side reactions have been
grouped in two different pathways that describe the formation of defect structures on going
from one amine generation to the next (see Scheme 1). One pathway accounts for incomplete
cyanoethylations and retro-Michael reactions, the other pathway accounts for intramolecular
amine formations (cyclizations).[22] With the ESI-MS spectra of all five generation
poly(propylene imine) dendrimers in hand, the significance of both pathways has been
calculated using an iterative computing process. Thus, every MS spectrum has been
simulated. The simulation indicates a polydispersity (Mw/Mn) of 1.002 and a dendritic purity
of ca. 23% for the fifth generation poly(propylene imine) dendrimer. Since the perfect
structure is the dominant species in the final product, it seems more appropriate to discuss the
mixture in terms of dendritic purity than in terms of polydispersity (the dendritic purity is
defined as the percentage of dendritic material that is defect-free).
ESI-MS studies on PAMAM dendrimers indicate defect structures arising from retro-
Michael additions and intramolecular lactam formations.[21] For a fourth generation
PAMAM dendrimer (48 end groups), a polydispersity of 1.0007 has been reported.[21a]
Interpretation of the published data reveals, however, a dendritic purity of at most 8%.
MALDI-MS studies on other divergently produced higher generation dendrimers (i.e.,
Newkome-type dendrimers[23] and carbosilanes[24]) have also shown the presence of small
numbers of imperfect structures. Metallodendrimers that have been studied with L-SIMS,[25]
MALDI-MS,[16] and ESI-MS[26] are of lower generations, and consequently, these
materials hardly contain defect structures, even though these materials have been produced in
a divergent approach. Reinhoudt et al. have synthesized a third generation Pd(II) dendrimer
with no observable defects in the mass spectrum.[27]
Dendrimers synthesized via the convergent approach can be produced nearly pure, as
confirmed by MS data. MALDI mass spectra of Fréchet-type dendrimers display very limited
amounts of impurities.[28] Moore’s phenylacetylene dendrimers have also been investigated
with MALDI mass spectrometry.[29] For a dendrimer with a mass of 39 969 D, almost no
impurities have been found.[30] ESI-MS data on carboxylate-terminated phenylacetylene
dendrimers subscribe the high degree of purity that can be attained for these
dendrimers.[28,29]
The detailed mass studies that have been devoted to the characterization of dendrimers
indicate the most important difference between both synthetic methodologies at hand. The
polymeric nature of the divergent approach results in an accumulating number of statistical
defect structures for every next generation. The defects are the result of the many reactions
that have to be performed on the same molecular fragment. Furthermore, almost no
possibilities exist for the purification of intermediate generations. The exponential growth in
the number of reactions to be performed on higher generations makes it virtually impossible
to produce perfect dendrimers of generations beyond five or six. Virtually no perfect
structures will be present in even higher generation materials. The organic nature of the
convergent approach results in defect-free dendrimers due to the limited number of reactions
performed on the same molecule on going from one generation to the next. Additionally, it is
possible to purify intermediate generations.
The small differences in structural features of the divergently produced structures on one
hand and the convergently synthesized structures on the other are not expressed in differences
in overall properties of these two classes of dendrimers (for example, all investigated
dendrimers show a maximum in the intrinsic viscosity as a function of their molecular
weight). Therefore, dendrimers, regardless the way in which they have been prepared, can
indeed be considered as the synthetic macromolecules with the most defined or most perfect
primary structure known today.
5. DENDRIMERS VERSUS LINEAR MACROMOLECULES

Dendrimers are monodisperse macromolecules, unlike linear polymers. The classical
polymerization process which results in linear polymers is usually random in nature and
produces molecules of different sizes, whereas size and molecular mass of dendrimers can be
specifically controlled during synthesis. Because of their molecular architecture, dendrimers
show some significantly improved physical and chemical properties when compared to
traditional linear polymers.
When dendrimers in solution are considered, the occupied volume of a single molecule
increases cubically with generation, whereas its mass increases exponentially. This typical
growth pattern of dendritic molecules determines their solution properties and makes these
properties deviate from those of linear molecules, especially at higher molecular weights. The
intrinsic viscosity is a physical parameter for which such a deviation has been measured. In
contrast to linear polymers (that obey the Mark-Houwink-Sakurada equation), the intrinsic
viscosity of dendrimers is not increasing with molecular mass but reaches a maximum at a
certain dendrimer generation (for polyaryl ether,[3a] poly(propylene imine),[31] and
PAMAM dendrimers,[32] these maxima have been reported).[33,34] Also in the solid state,
the growth pattern of dendrimers determines their physical characteristics. In general, it is
believed that a gradual transition in overall shape, from a more extended arrangement for
lower generation dendrimers to a compact and approximate globular shape for higher
generation dendrimers, causes the deviation in physical behavior of dendrimers from those of
linear macromolecules.
Fréchet et al. have studied several physical properties of polyether and polyester
dendrimers.[35] The increase in glass transition temperature (Tg) of the dendrimers levels off
at higher molecular weights, a phenomenon that is also observed for the linear analogues. For
linear polymers in general, a leveling off of the Tg increase has been known for a long time,
and this effect is explained by the declining influence of the end groups and the role of the
entanglement molecular weight. Dendrimers have more end groups at higher masses, but, as
opposed to linear macromolecules, dendrimers are not significantly entangled. The absence of
entanglements in the higher generation materials is subscribed in a study on the melt
viscosities of polyether dendrimers.[36] In another study by the same authors, it appears that
the melt viscosity is a physical parameter that is very dependent on the type of end group in
the dendrimer.[37]
Miller et al. have compared the solubilities of 1,3,5-phenylene-based dendrimers with
those of oligo-p-phenylenes.[38] Although m-phenylenes would have been more appropriate
linear analogues, the study shows that the dendrimers have an enhanced solubility. Similar
results have been obtained by Fréchet et al. who have compared dendritic polyesters with
their linear counterparts.[39] In contrast to the linear polyesters, the dendrimers are soluble in
a vast range of organic solvents. The authors also note a marked difference in reactivity: the
debenzylation of the polyesters via catalytic hydrogenation on Pd/C is only possible for the
dendritic structures. Differences in solubility and reactivity have also been found between
poly(propylene imine) dendrimers with nitrile end groups and poly(acrylonitrile). The nitrile
dendrimers are soluble in various organic solvents, whereas their linear analogues are
crystalline and only soluble in very polar solvents such as dimethylformamide and
concentrated sulfuric acid. Due to this limited solubility, the catalytic hydrogenation of
poly(acrylonitrile) is not possible, while dendritic polynitriles are easily hydrogenated.[31,40]
For all these cases, the observed differences in solubility and reactivity have been attributed
to the globular architecture of the dendrimers and the accessibility of the end groups of the
dendrimer.
The uniqueness of dendritic architectures has been shown in an elegant study by Hawker
et al. in which polyether dendrimers are compared with their linear isomers (Figure 2).[41]
Especially the fifth and sixth generation dendrimers display differing features when compared
to their structural isomers. The hydrodynamic volume of the fifth generation polyether
dendrimer is approximately 30% smaller than that of its linear analogue. The difference is
ascribed to a more compact backfolded globular structure of the dendrimer. In addition, the
fifth generation dendrimer is completely amorphous (a Tg of 42 °C is recorded) and is soluble
in a variety of organic solvents, whereas the linear analogue is highly crystalline and poorly
soluble in THF, acetone, and chloroform. The Hawker investigation solidly confirms that the
physical behavior of dendrimers is different from that of linear polymers, and equally
important, it shows that dendrimers need to have a certain size to display significantly
different physical behavior.
Figure 2. The fourth generation polyaryl ether dendrimer and its linear isomer.
6. APPLICATION OF DENDRIMERS
6.1. Asymmetric Transfer Hydrogenation
6.1.1. Asymmetric Transfer Hydrogenation to Olefins

The first attempts to carry out asymmetric catalysis using chiral metallodendrimers were
reported by Brunner’s group. These reports belong to the pioneering works in catalysis using
metallodendrimers that appeared in 1994. Brunner designed dendritic catalysts containing
dendritic phosphines which he called “dendrizyme” because of their hoped for similarities
with enzymes.[42] Brunner et al. reported on a complex synthesized from a diphosphine core
and dendritic branches containing menthyl groups (Figure 3).[43] The ligand was
coordinated to RhI in situ by reaction with [Rh(η4-COD)Cl]2. Application of the rhodium
complex (Rh:substrate ratio 1:50) to the hydrogenation of acetamidocinnamic a cid after 20 h
at 20 bar H2 pressure led the desired product with a small enantioselectivity (enantiomeric
ratio of 51:49).[44] A very interesting feature of this early study, however, is that the rate of
hydrogenation was higher in the presence of the dendritic diphosphine ligand having the
dendritic wedge located at the meta position of the arene rings than with the nondendritic
dppe. This spatial arrangement had a crucial role since, on the other hand, hydrogenation with
a dendritic diphosphine having dendritic wedges in 2,5-position exhibited a 300-fold rate
decrease while the enantioselectivities remained very weak.
Figure 3. Brunner’s dendrizyme ligands reported in 1994 for the hydrogenation of acetamido cinnamic
acid ( Rh-dendritic dppe ligang).
Figure 4. Kakkar’s organophosphie dendrimers with phosphorous atoms at the focal points (up to P46 on
the figure).
Kakkar’s group reported on an interesting organophosphine dendrimers with phosphorus

atoms at the focal points (Figure 4).[45] The divergent construction involved reaction of
(CH3)3SiNEt2 with P{(CH2)3OH}3 followed by sequential reactions of the dendrimer with
these two reagents successively up to the P46 dendrimer. The metallodendrimers containing
[RhCl(η4-1,5-C8H12)PR3] moieties were best synthesized by reactions of these phosphorus
dendrimers with [Rh(μ-Cl) (η4-1,5-C8H12)]2 and were shown to catalyze the hydrogenation of
1-decene in a 1:200 metal-to-substrate ratio (25 °C, 20 bar H2, 30 min, THF). The catalytic
activity (turnover number about 200 molprod (molcat)-1 and turnover frequency about 400
molprod (molcat)-1 h-1) was found to be similar to that of the monometallic complex. There was
a slight decrease in turnover frequencies upon growth of the RhI46 dendrimer. After one such
cycle of hydrogenation using the Rh46 dendritic catalyst, the organic product was extracted
into pentane and the Rh46 dendrimer was recrystallized from THF/hexane mixtures and reused
with only 5% decrease in conversion, which favorably compares with supported catalysts.[45]
Mizugaki et al. examined the selective hydrogenation of conjugated dienes to monoenes
using an atmospheric pressure of H2 at 25 °C by the dendritic catalyst DAB-dendr-
[N(CH2PPh2)2PdCl2]16 prepared by reaction of Reetz’s dendritic phosphine (vide infra) with
[PdCl2(PhCN)2].[46] The excellent selectivity of the hydrogenation of cyclopentadiene to
cyclopentene is remarkable. The catalytic activity was higher than that of the corresponding
monomer [PdCl2{PhN(CH2-PPh2)2}] and the polystyrene-bound catalyst. The
metallodendrimer was less active than Pd/C and Pd/Al2O3, but these heterogeneous catalysts
are not selective contrary to the dendritic catalyst. Another remarkable feature of this system
is that the hydrogenation of 1,3-cyclooctadiene by the same dendritic-PdCl2 complex
occurred with much higher rates than by the monometallic catalyst. Interestingly, this reaction
was very efficient in ethanol in which the dendritic catalyst was not soluble whereas it was
slow in DMF in which it was soluble. Thus, heterogeneization renders the system efficient.
Rationalization of all these features would be speculative, but it seems that the active metallic
sites are well accessible on the surface of the heterogeneous catalyst. The dendritic catalyst
was easily recovered from reaction mixtures by centrifugation and reused without much loss
of activity.[46]
Togni et al. decorated 8-, 12-, and 16-branch dendrimers with ferrocenyldiphosphine
ligands and also synthesized the corresponding rhodium(I) complexes (Figure 5).[47] These
ferrocenylphosphine-rhodium(I) dendrimers catalyze the hydrogenation of dimethylitaconate
(1) affording the desired product 2 (Scheme 2) with an enantioselectivity (ee) of 98%, which
compares with the ee of 99% obtained for the monomeric Josiphos catalyst. Moreover, the
dendritic catalyst can be separated from the reaction mixture using a nanofiltration
membrane.[47]
The Fan and Chan groups reported a series of dendritic BINAP ligands with Fréchet-type
polyether wedges and their ruthenium complexes as catalysts in asymmetric hydrogenation of
2-[p-(2-methylpropyl)phenyl]acrylic acid in methanol-toluene (1:1, v/v) at 50 °C. The
dendritic BINAP-Ru catalysts showed slightly higher enantioselectivity (ee = 92.6% with
100% conversion in 20 h) than Ru-BINAP (ee = 89.8%). The catalyst could be precipitated at
the end of the reaction and then reused three times without loss of activity or
enantioselectivity.[48]
Figure 5. Example for Tongi dendrimers with optically active ferrocenyldiphosphine ligands.

O O Chiral dendritic catalyst O O
O O H2 O O
1 2
(ee = 98%)
Scheme 2. Hydrogenation of dimethylitaconate.
In an interesting approach, the first effort for the preparation of Pd-Rh bimetallic
nanoparticles in the presence of poly(amidoamine) dendrimers with surface hydroxyl groups
(fourth generation, PAMAM-OH) has been reported by Rhee et al.[49] Schematic illustration
for the preparation of dendrimer-encapsulated bimetallic nanoparticles is represented in
Scheme 3.
Scheme 3. Schematic diagram for the preparation of dendrimer encapsulated Pd-Rh bimetallic
nanoparticles.
The dendrimer-encapsulated Pd–Rh bimetallic nanoparticles were applied as catalyst to

the partial hydrogenation of 1,3-cyclooctadiene in ethanol/water mixture (v/v = 4/1). As
shown in Figure 6, the dendrimer-encapsulated Pd–Rh bimetallic nanoparticles were found to
be effective in the hydrogenation reaction.[49] Different from the conventional polymer
stabilized nanoparticles, the dendrimer-encapsulated nanoparticles are confined primarily by
steric effects and therefore a substantial fraction of their surface is unpassivated and available
for reactant to access in catalytic reactions. It is worth noting, however, that there exist
apparent differences between two systems. While bimetallic nanoparticles with Pd content of
80% showed the highest activity in the case of Pt-Pd, the highest activity was achieved with a
Pd/Rh ratio of 1/2 in Pd–Rh system as shown in Figure 6. The cyclooctene selectivity at the
complete conversion of 1,3-cyclooctadiene was higher than 99%, which is as high as that of
the palladium or rhodium nanoparticle catalyst. In order to confirm the feasibility of catalyst
recycling, after a reaction was completed, the catalyst was reused. It was found that the
reaction performance was as good as that of the fresh one. This indicates that the dendrimer-
encapsulated Pd–Rh bimetallic catalyst can be recycled and reused without a significant loss
of its catalytic activity.
Figure 6. Dependance of the catalytic activity of dendrimers encapsulated Pd-Rh bimetallic

nanoparticles on its composition in the partial hydrogenation of 1,3-cyclooctadiene.
Gade et al. have been reported on the synthesis of a series of chiral phosphine
functionalized poly(propyleneimine) (PPI) dendrimers by the reaction of carboxyl-linked C2-
chiral pyrphos ligand (pyrphos=3,4-bis(diphenylphosphino)pyrrolidine) with zeroth fourth
generation PPI using ethyl-N,N-dimethylaminopropylcarbodiimide (EDC)/1-
hydroxybenzotriazol as a coupling reagent.[50] Metallation of the multi-site phosphines with
[Rh(COD)2][BF4]cleanly yielded the cationic rhododendrimers containing up to 32 metal
centers (for the fourth generation species). The relationship between the size/generation of the
dendrimer and its catalytic properties was established in the asymmetric hydrogenation of Z-
methyl-α-acetamidocinammate and dimethylitaconate. A decrease in both activity and
selectivity of the synthesized rhododendrimers dendrimers was clearly observed on going to
the higher generations.
Moreover, an efficient strategy for the backbone functionalization of a tripodal phosphine
ligand which allows its attachment to carbosilane dendritic supports has been developed by
Gad et al.[51] These dendrimers were metallated with four and eight molar equivalents of
[Rh(COD)2][BF4] in CH2Cl2, selectively yielding the desired metallated dendrimers.
Comparative catalytic hydrogenation of styrene and 1-hexene using the metallodendrimers
showed that the fixation to the low generation dendrimers did not alter the catalytic
hydrogenation properties of the catalysts.
Maarseveena et al. have been reported on the functionalization of the axially chiral
BICOL backbone with two third generation carbosilane dendritic wedges and further
elaborated to a phosphoramidite ligand. The chiral ligands 5 and 7 were prepared as shown in
Schemes 4 and 5.[52]
H CH3
N N .
i) MeI, NaH
ii) TBAF O CH3
OR
P N
OR iii) HMPT O CH3
(95%)
N N
H CH3
3. R = J (R)-BINOL) (R)-5
TBSL, Et3N (100%)
4. R = TBS
Scheme 4. Synthesis of physphoramidite ligand 5 from (R)-BINOL.
Scheme 5. Synthesis of dendritic chiral ligand 7.

The rhodium-catalyzed asymmetric hydrogenation of methyl 2-acetamidocinnamate 8

was used as the model reaction to study the catalytic behaviour of the new ligands (R)-5 and
(R)-7 (Scheme 6 and Table 1). High enantioselectivities (up to 95% ee) were obtained when
these monodentate ligands were applied in the rhodium-catalyzed asymmetric hydrogenation
of methyl 2-acetamidocinnamate. When a ligand to rhodium ratio of 2.2 was used, the
enantioselectivity induced by the rhodium complex based on ligand 3 (entry 3) was 93% (at
full conversion). This shows the ability of the bicarbazole skeleton to induce high
enantioselectivity. The catalytic behaviour of the dendritic analogue 5 was similar; in 2.5 h,
product 8 was obtained quantitatively with an enantiomeric excess of 95% (entry 4).
Rh(COD)2BF4 (1 mol%)
(R)-Ligand
H2 (5 bar)
AcHN COOMe CH2Cl2, room temp. AcHN COOMe
8 9
S
Scheme 6.
Table 1. Asymmetric hydrogenation of methyl-2-acemtamidocinnamate 8.
Entry Ligand Ratio L/Rh t (h) Conv. (%)a ee (%)b
1 Mono Phosph 2.2 2.0 100 95

2 Mono Phosph 3.0 2.0 0 ---
3 5 2.2 2.5 100 93
4 7 2.2 2.5 100 95
5 7 3.2 2.5 100 95
6 7 4.2 2.5 ~30 90
a)
Determined by 1H NMR.
b)
Determined by chiral HPCL (Diacel OD, heptanes-isporpanol=9:1)
It is worth to mention that the Leeuwen group has examined the activity of Rh complexes
of the dppf-type dendritic ligands in the hydrogenation of dimethylitaconate in a continuous-
flow membrane reactor. This shows a reasonable constant of formation of the product
compared to the non-dendritic catalyst.[52,53]
Fan and co-workers have been reported on the synthesis of a class of dendritic
monodentate phosphoramidite ligands through substitution of the dimethylamino moiety in
MonoPhos by the Fréchet-type dendritic wedge and their application in the asymmetric
hydrogenation of α-dehydroamino acid esters and dimethylitaconate. The dendritic chiral
ligands 10a-c were prepared in moderate yields. For comparison, a model compound of a
small molecule 11 was also synthesized (Figure 7).[54]
The rhodium-catalyzed asymmetric hydrogenation of methyl 2-acetamidocinnamate was
first used as the model reaction to study the catalytic behavior of the dendritic ligands 10 and
11. The rhodium catalysts were prepared in situ by reaction of 2 equiv of the appropriate
dendrimer ligands with [Rh(COD)2][BF4]in dichloromethane at room temperature. Typically,
the reactions were carried out at room temperature in dichloromethane as the solvent. All
catalysts gave high enantioselectivities (up to 97.9% ee), which are better than that obtained
from Mono-Phos 11 (95%).[54,55] These results indicated that the size of the dendritic
substituents on the nitrogen atom would not result in any negative effect on the selectivity,
which is in contrast to the results obtained with the corresponding small monodentate
phosphoramidite ligands bearing different substituents on the nitrogen atom.[54,56]
Ph
O O
N N
O
P P
O O
O O
O
O 11
n
10a. (n= 0); 10b. (n= 1); 10c. n= 2)
Figure 7.
The same authors applied the same dendritic catalysts to the hydrogenation of other α-
dehydroamino acid ester substrates.[54] Excellent enantioselectivities (up to 97.9 ee) were
also achieved in all cases, which are better or comparable to those obtained from Mono-Phos
11. Hydrogenation of substrates with electron donating and withdrawing meta- or para-
substituents on the phenyl group gave slightly higher ee values as compared to the ortho-
substituted substrates. It was noted that the dendritic catalysts showed slightly higher
enantioselectivities for all ortho-substituted substrates than those obtained from the monomer
ligand 11. Hydrogenation of dimethylitaconate also gave excellent enantioselectivities, which
are better than those of Mono-Phos).[54,55]
Figure 8.
Carbosilane dendrimers (12-14; Figure 8) containing P-stereogenic monophosphines as

terminal groups, Dend-{CH2PPhR}n (R=2-biphenylyl or 9-phenanthryl) were prepared.[57]
The rhododendrimers Dend-{CH2PPhR(RhCl(COD))}n were cleanly obtained by reacting
[RhCl(COD)]2 with the corresponding dendrimer in CH2Cl2 at room temperature.

Recrystallization in CH2Cl2/diethyl ether gave the targeted rhododendrimers as yellow solids
in good yields. They are soluble in most common organic solvents and were characterized by
elemental analyses, 1H, 13C and 31P NMR spectroscopy, and ES mass spectrometry. The
catalytic properties of the rhodium dendrimers were tested in the hydrogenation of
dimethylitaconate. The model chiral compounds, (CH3)3Si{CH2PPhR(RhCl(COD))} and
(CH3)3Si{CH2PPhR(RuCl2(p-cymene))}, were prepared in order to detect potential dendritic
effects. All compounds were found to be active in the catalytic conditions tested, but low or
null ee were found.[57]
Fan et al have been recently designed and synthesized a new kind of dendritic pyrphos
ligands bearing alkyl chains at the periphery for the Rh-catalyzed asymmetric hydrogenation
of dehydroamino acids.[58] The new series of dendritic ligands with a chiral diphosphine
located at the focal point have been synthesized through coupling of (R,R)-3,4-
bis(biphenylphosphino)pyrrolidine (pyrphos) with peripherally alkyl-functionalized benzoic
acid dendrons (Scheme 7).
H3C H2C H3C H2C

n O nO
PPh2 O PPh2
(i)
H3 C H 2C O
n
COOH + HN H3C H2C O
n
C N
PPh2 PPh2
O O
H3C H2C H3C H2 C
n
n
15C-G1, n = 9
16C-G1, n = 15
H3C H2C H 3C H2C
9 O 9
O
H 3C H 2C H3C H2C
9
O 9
O
O O
O PPh2 H3C H2C O
H3C H 2C O PPh2
+
9 (i) 9
COOH HN C N
PPh2 PPh2
H3C H2C O H3C H2C O
9 O 9 O
O O
H 3C H 2C H3C H2C
9 9
O O
H3C H2C (i) DCC, DMAP, CH2Cl2, r.t. H3C H2C
9 9
17C-G2
Scheme 7. Synthesis of chiral deneritic pyprophos lignads.
With these chiral dendritic catalysts, the asymmetric hydrogenation of

acetamidocinnamic acid (18) as a standard reference system for comparing their catalytic
performance (Scheme 8).[58]
Scheme 8.
As it was expected, the number and length of the alkyl end groups of the dendritic
wedges influenced the reaction performance and the results depended on the solubility of the
dendrimer in solvent. Full conversion and high enantioselectivity (up to 95.6% ee) for the first
generation dendrimer ligand 15C-G1 was observed, which are similar to those previously
reported for the soluble polymer-supported catalyst (95.5% ee). Interestingly, full conversion
and high enantioselectivity (up to 97.8% ee) were observed in case of using dendrimer ligand
17C-G2.[58,59]
It was found that these dendrimer-based catalysts with alkyl tailed at the periphery
preferred to dissolve in a non-polar solvent system. In the case of the second-generation
dendritic ligand 17C-G2, more than 99% of its Rh complex could be extracted to the non-
polar cyclohexane phase in a methanol/cyclohexane (2.0% H2O) biphasic system. The
cyclohexane layer, which contained the catalyst 17C-G2-Rh(I), was separated and reused in
the next run of reaction. The recovered catalyst was reused five times with similar
enantioselectivity, albeit decreased activity until the fourth cycle (Table 2, entry 4).[58,60]
Table 2. Recycling of the catalyst 17c-G2-RH (I) in the asymmetric hydrogenation of

acetamidocinnamic acid 18.
Entry Cycle Conv. (%) ee (%)

1 First 100 97.0
2 Second 99 97.1
3 Third 97 97.0
4 Fourth 83 96.8
5 Fifth 56 95.5
6.1.2. Asymmetric Transfer Hydrogenation to Ketones and Imines

The chiral diamine core was discovered by Noyori for the catalysis of asymmetric
transfer hydrogenation of acetophenone which [RuCl2(η6-cymene)]2 is the Ru source and is
available on the kilogram scale.[61] The dendrimers rather favorably compare with the parent
nondendritic catalyst in terms of activity, and the enantioselectivity was retained. It was
remarkable that, upon recycling the dendritic catalyst, the enantioselectivity was retained
while the activity only decreased slightly.
Deng et al. have been reported on the synthesis of multiple dendritic ligands 20-22 based
on (R,R)-1,2-diphenylethylenediamine in a convergent approach (see Figure 9).[62] Their
ruthenium complexes prepared in situ had good solubility in the reaction medium (azeotrope
of formic acid and triethylamine). Initial experiments were conducted to test the
catalytic activity of ruthenium(II) complexes of the dendritic ligands in the
asymmetric transfer hydrogenation reaction of acetophenone which was used as the
model substrate and the azeotrope of formic acid and triethylamine as the hydrogen source.
Ru(II) complexes of (R,R)-TsDPEN (23) and (R,R)-N-(4-acetylaminophenylsulfonyl)-1,2-
diphenylethylenediamine (24) were selected as monomeric catalysts for comparison.[62]
It was found that the macromolecular catalysts showed no significant difference in
activity and enantioselectivity in the asymmetric transfer hydrogenation of acetophenone as
compared with the monomeric catalysts 23 and 24. Good retention of catalytic activity and
high enantioselectivity were observed in these dendritic catalysis. However, the glycine
spacer had mild negative effects on the catalytic activity (entries 3 vs 4; Table 3).
Ph Ph
O O
R S NH NH2
C O
O 4
20. R = NH
21. R = NHCOCH2CHNH2
22. R = H
Figure 9.
Table 3. Comparison of Dendritic and Monomeric Catalysts in Asymmetic Transfer

Hydrogenation of Acetophone a.
a
Reactions were conducted at 28oC for 20h. S/C=100.
b
Conversions were determined by GC.
c
The average TOFs were calculated over the 5h reaction time.
d
Determined by GC with a Chrompack CP Chirasil-dex column (25m x 0.25mm).
For exploring the scope and limitations of this reaction catalyzed by the dendritic
catalysts, a variety of ketones and imines (see Figure 10) were applied in the asymmetric
transfer hydrogenation with HCOOH-NEt3.[62] In general, excellent conversions with
quantitative yields and for some cases a slightly higher enantioselectivities (up to 98.7% ee)
were obtained using the dendritic catalysts. Considering the high local catalyst concentrations
at the periphery, diones were tested for the possible synergic reactivity between catalytic units
at the surface, while no apparent differences were noted.[62]
O O O O O
O O Ph
S S P
N N Ph
n N O
a. R = o-F R
b. R = p-F a. n = 1 a. R = Bn
c. R = o-Cl b. n = 4 b. R = But
d. R = o-Br
e. R = p-Br
Figure 10.
Scheme 9. Synthesis of dendronized poly(BINAP)s.
Fan et al. reported on the synthesis of a new kind of dendronized polymeric chiral BINAP
ligands and applied to the Ru-catalyzed asymmetric hydrogenation of simple aryl ketones and
2-arylacrylic acids. The dendronized poly(BINAP) ligands were synthesized as shown in
Scheme 9.[63] These dendronized poly(Ru-BINAP) catalysts exhibited high catalytic activity
and enantioselectivity, very similar to those obtained with the corresponding parent
Ru(BINAP) and the Ru(BINAP)-cored dendrimers. It was found that the pendant dendrons
had a major impact on the solubility and the catalytic properties of the polymeric ligands.
These polymeric catalysts could be easily recovered from the reaction solution by using
solvent precipitation, and the reused catalyst showed no loss of activity or
enantioselectivity.[63]
The catalytic efficiency of the dendronized poly(Ru-BINAP) catalytic system was further
demonstrated in the asymmetric hydrogenation of 2-arylacrylic acids.[63] The Ru catalyst
was prepared by mixing [Ru(benzene) Cl2]2 and the appropriate polymeric ligand in situ in
hot DMF. High enantioselectivities were obtained in the asymmetric hydrogenation of 2-[p-
(2-methylpropyl)phenyl]acrylic acid and 2-phenylacrylic acid (82-83% ee), which were
comparable to those obtained with Ru(BINAP) under otherwise identical reaction conditions.
It was found that the size of the pendant dendrons also slightly influenced the
enantioselectivity of the polymeric catalysts.[63]
It is importantly to note that the Ru catalyst with the third generation pendant dendrons
was used for the recycling experiments. Upon completion of the reaction, methanol was
added to the reaction mixture and the catalyst was quantitatively precipitated and recovered
via filtration. The recovered catalyst was reused for at least three cycles in the asymmetric
hydrogenation of 2-methylacetophenone with similar enantioselectivity (~92% ee).[63]
Hydrophobic Fréchet-type dendritic chiral 1,2-diaminocyclohexane-Rh(III) complexes
have been prepared and applied in the asymmetric transfer hydrogenation of ketones in water
using HCOONa as hydrogen source.[64] The core-functionalized dendritic ligands 29a-d
based on chiral 1,2-diaminocyclohexane (DACH) were smoothly prepared as illustrated in
Scheme 10. The dendritic structures could be established through MS techniques (ESI HRMS
or MALDITOFMS).
Scheme 10. Synthesis of dendritic DACH ligands.
With the desired chiral dendritic ligands 29a-d, the catalytic activity and
enantioselectivity of their ruthenium or rhodium complexes were studied via the transfer
hydrogenation of acetophenone, and also compared with the monomeric TsDACH-metal
complex.[63,64] The transfer hydrogenation reactions was conducted in three different
conditions for detailed comparison of the dendritic catalysis at 1 mol% catalyst loading: (a)
[RuCl2(cymene)]2 as the metal precursor in DCM solution, the azeotrope of HCOOH–NEt3 as
the hydrogen source at 28 ◦C; (b) [RuCl2(cymene)]2 as the metal precursor in aqueous
solution, HCOONa as the hydrogen source at 35 ◦C; (c) [RhCp*Cl2]2 as the metal precursor
in aqueous solution, HCOONa as the hydrogen source at 40 ◦C.
Although quite different results were obtained under the above-mentioned three reaction
conditions, in general, good retention of high enantioselectivity was observed for all dendritic
catalysts as compared to the monomeric metal TsDACH-metal complex. It is worth to
mention that the reduction of acetophenone took place smoothly at 0.1 mol% of 29b–Rh(III),
furnishing a >99% conversion with 94% ee in 4 h.[64] The recyclability of these dendritic
catalysts was then tested via the solvent precipitation method. The second generation
dendritic 29b–Rh(III) complex at 1 mol% loading was employed in the transfer
hydrogenation of acetophenone, as the example. The recycling use of dendritic 29b-Rh(III)
catalyst was quite successful and excellent conversion (97%) and enantioselectivity (95% ee)
were obtained even in the sixth run with some extension of the reaction time.[64]
Subsequently, the above-mentioned protocol was extended to a range of aromatic, hetero-
aromatic and functionalized ketones (Figure 11), aiming to determine the potential
applicability of the dendritic catalytic system in the asymmetric transfer hydrogenation in
water. Excellent conversions (up to >99%) and high enantioselectivities (up to 97% ee) could
be obtained.[64]
Figure 11. Structures of various ketones.
Deng et al. have been reported on the synthesis of tunable dendritic N-monosulfonyl
ligands via direct N-monosulfonylization of the chiral dendritic vicinal diamines. The chiral
dendritic N-arylsulfonyldiamine ligands (R,R)- and (S,S)-30 that are shown in Figure 12 were
prepared in good to high yields (65-85%). The application of these dendritic ligands in the
asymmetric transfer hydrogenation of ketones was investigated. For comparison, a
monomeric ligand, (R,R)-31 was also prepared.[65] The asymmetric transfer hydrogenation
was first studied using acetophenone as the model substrate. Compared to the complexes of
monomeric ligand (R,R)-31, as well as TsDPEN, a slightly enhanced reactivity was observed
for the dendritic catalysts, Ru[(R,R)-30] with similar enantioselectivities which are more
active than those dendritic catalysts derived from amino-functionalized vicinal diamine (the
TOF values are less than 12). However, when the third generation catalyst of Ru[(R,R)-30]
was used, the reactivity had a notable drop in only 75% conversion (TOF value is 4.3) along
with a slight decrease of enantioselectivity with the same reaction time. In general, the
hydrogenated product was obtained with high yields (conversion was >99%) and high
enantioselectivities up to 97.5% ee. Interestingly, the second generation catalyst of Ru[(R,R)-
30] could be recovered by precipitation with an addition of methanol after removed of DCM
under reduced pressure and reused four times with slightly higher enantioselectivities (97.5,
97.2, 97.5 and 97.0% ee vs 96.1% ee).[65]
Several aliphatic and aromatic ketones as substrates were also examined in the
asymmetric hydrogenation reaction using the dendritic catalysts (R,R)- and (S,S)-30. In
general, the conversions of ketones and enantioselectivities of the reduced products did not
obviously change when using dendritic (R,R)- and/or (S,S)-30 as a ligand compared to the
monomeric ligand (R,R)-31 and TsDPEN. The above-mentioned study showed an increase of
enantioselectivities in the asymmetric reduction could be achieved by fine tuning of the
coordinating amino group NH2 of chiral 1,2-diamines.[65]

O
O
O
1
R HN * n
MeO OMe
R2HN *
O
O
H2N NHSO2C6H4-p-CH3
O
n
(R,R)-31
(R,R)- and (S,S)-30
Figure 12.
Fan and Shuai have been reported on the synthesis of a series of new chiral dendritic
BIPHEP ligands and their applications in the Ru-catalyzed asymmetric hydrogenation of β-
ketoesters were investigated.[66] The authors chose enantiopure MeO-BIPHEP as the starting
compound to make the dendritic BIPHEP ligands 35a-c. The synthetic procedure is outlined
in Scheme 11.

O O
Br n
O n O
O O
HO PPh2 HO PPh2 O PPh2 c
a 33 (R)-35
HO PPh2 95 % b O PPh2 n=1, 35a, 84%
HO PPh2
O n=2, 35b, 99%
O O n=3, 35c, 99%
32
n
O
n=1, 34a, 55%

O n=2, 34b, 50%
PhCH2O PPh2 e
PhCH2O PPh2 n=3, 34c, 60%
d
32
50% PhCH2O PPh2 70% PhCH2O PPh2
O
36 37
Scheme 11. Synthesis of dendritic BIPHEP Regents and conditions. (a) H2O2 (35%), CH3OH 2h at r.t;
(b) 33, K2CO3, acetone, reflux; (c) NEt3/NBu3, toluene, reflux; (d) benzl bromide, K2CO3, acetone,
reflux.
In order to evaluate the catalytic efficiency of these dendritic ligands and the influence of
the dendritic wedges on the enantioselectivity of a given reaction, the well-studied
asymmetric hydrogenation of β-ketoesters was selected as the standard reactions (Scheme
12). The Ru-catalyst was prepared by mixing [Ru(benzene)Cl2]2 and the proper dendrimer
ligand in situ in hot DMF. The reaction was carried out in a CH2Cl2-ethanol mixture as the
solvent under 40 atm of H2 pressure at 60 ◦C for 24 h. For comparison, the model ligand 37
was performed under the same reaction conditions.[66]
O O OH O
Dendritic Ru(BIPHEP), H2
R1 OR2 R1 * OR2
CH2Cl2/ C2H5OH (1:1)
Scheme 12. Asymmetic hydrogenation of B-ketoester catalyzed by dendritic Ru (BIP HEP) catalysts.
While all dendritic catalysts showed similar reactivity, the enantioselectivity varied
dramatically with increase in generation from 1 to 3. For example, methyl 3-oxo-3-
phenylpropanoate was reduced with ca. 93.1% ee using the model small molecule Ru(37)
catalyst. The enantioselectivity decreased to 92.0% ee with the first generation Ru(35a)
catalyst and reached a minimum of 86.6% ee with the second generation Ru(35b) catalyst.
Unexpectedly, with further increase of generation to 3, enantioselectivity increased slightly to
91.3% ee. This result indicated that similar catalytically active Ru-complex of Ru(35c) was
formed under the reaction conditions despite the bulky dendritic substituents. This general
trend was found to be true for all substrates used in this study.[66]
It has been recently reported that the asymmetric hydrogenation of quinolines catalyzed
by chiral dendritic catalysts derived from BINAP gave the corresponding products with high
enantioselectivities (up to 93%), excellent catalytic activities (TOF up to 3450 h-1), and
productivities (TON up to 43 000).[67] Fréchet-type polyaryl ether dendrons were chosen for
this study owing to their chemical inertness and inability to coordinate iridium. The synthetic
pathway and structures of the dendritic ligands are shown in Scheme 13.
Scheme 13. Synthesis and Structures of Dendritic GnDenBINAP Ligands.

The effects of the solvents, temperature, hydrogen pressure, and additive on the activity
and enantioselectivity were investigated by using the second-generation dendrimer catalyst,
which was generated in situ from G2DenBINAP and [Ir(COD)Cl]2 (Table 4). A series of
organic solvents were tested, and THF was found to be the best choice in terms of both
conversion and enantioselectivity (entries 1-5). The enantioselectivity of the reaction was
slightly increased at low temperature, but the reaction could be completed at prolonged time
(entry 8). Notably, low conversion and enantioselectivity were observed under both higher
and lower hydrogen pressure (entries 9 and 10). The reaction could not proceed without
iodine as an additive (entry 13).[67]
Table 4. Asymmetric Hydrogenation of Quinaldine (38a) Catalyzed by Dendritic Ir

(G2DenBINAP) Catalysta.
a
Reaction conditions: 0.25 mmol of quinaldine 38a in 1.25mL of solvent, 0.5 mol% of [Ir(COD)C1]2,
1.1.mol % of (S)-G2DenBINAP, I2/catalyst = 10 (mol/mol), 45 atm H2, 15-20oC.
b
Determined 1H NMR analysis of the crude product.
c
. Determined by HPCL anaylysis with Chirapak OJ-H column. The predominated product was in the S-
configuration.
d
Reaction temperature = 50oC
e
Reaction temperature = 0oC.
f
H2 = 100 atm.
g
H2 = 10 at,
h
I2/catalyst = 1 (mol/mol).
i
I2 = 0 mol %.
The applications of the dendritic catalyst in the asymmetric hydrogenation of other 2-

substituted quinoline derivatives using G2DenBINAP as the ligand were further investigated
(Table 5). In general, all substituted quinolines studied were hydrogenated with good
enantioselectivities and conversions.[67] The reaction was found to be relatively insensitive
to the length of the 2-alkylated side chain of quinolines, and high enantioselectivities and
good yields have been consistently obtained (entries 1-3). Notably, under low catalyst
loading, the reactions performed well, affording similar enantioselectivities, albeit low
catalytic activities (entries 1-7). The authors then investigated the recyclability.
G3DenBINAP-Ir-catalyzed asymmetric hydrogenation of 38a was chosen as the standard
reaction. Upon the completion of the reaction, the catalyst was quantitatively precipitated by
the addition of hexane and reused at least six times with similar enantioselectivities but at the
expense of relatively low catalytic activities.[67]
Tabel 5. Catalytic Asymmetric Hydrogenation of Quinoline Derrivativesa.
a
Reaction conditions: 0.25 mmol of substrate in 1.25 mL of THF 0.25 mol% of Ir(G2DenBINAP)
catalyst. 5 mol% of I2, 20-25oC, 1.5h.
b
Determined by 1H NMR analysis of the crude product.
c
Determined by HPCL analysis with Chirapak OJ-H (38a-c, 28i and 38j). AS-H 938d and 38e) and
OD-H (38f-h and 38k) columns.
d
The Absolute configuration is assigned by comparison of the HPCL retention time with those reported
in the literature data.
e
Data in brackets were obtained by usint 0.01% catalyst under the following conditions: 2.5 mmol of
substrate in 5 mL of THF, 1.125 mol% of I2, 20-25oC, h.
f
Reaction time =36h.
6.2. Hydroformylation
The hydroformylation reaction extensively used in research and industry, converts

terminal olefins, carbon monoxide, and hydrogen into linear or branched aldehydes (Scheme
14).[68] The homogeneous catalysis, mostly based on rhodium and cobalt complexes, is the
predominant approach to this process. However, during the last decade, there has been
growing interest in developing various catalytic systems for the reaction to successfully
recycle the expensive catalytic complexes.
CHO CHO
Catalyst
R
+ CO + H2 + R
R
Scheme 14. Hydroformylation reaction.
The Reek and van Leeuwen group synthesized diphenylphosphine-functionalized

carbosilane dendrimers Si{(CH2)nSi(CH3)2(CH2PPh2)}4 (n=2, 3; generations 1-3) and
Si{(CH2)nSi(CH3)(CH2PPh2)2}4 (n=2, 3; generation 1, 2). These chiral ligands were used for
the rhodium-catalyzed hydroformylation of 1-octene.[69] The diphenylphosphine
functionalized carbosilane dendrimers with both monodentate and bidentate end groups were
synthesized by hydrosilylation of the various generations of carbosilane dendrimers with
chlorodimethylsilane or dichloromethylsilane followed by a reaction with lithium
methyldiphenylphosphine-TMEDA (Scheme 15).[69,70]
i
Gx n Gx n Si Cl iv
m
m
40. x = 0, n = 0, m = 4 46. x = 0, n = 0, m = 4
41. x = 1, n = 0, m = 12 47. x = 1, n = 0, m = 12
42. x = 2, n = 0, m =36 Gx n Si PPh2 48. x = 2, n = 0, m =36
m 49. x = 0, n = 1, m = 4
43. x = 0, n = 1, m = 4
50. x = 1, n = 1, m = 12
44. x = 1, n = 1, m = 12 51. x = 2, n = 1, m = 36
45. x = 2, n = 1, m = 36 Cl v
Gx n Si
ii
m
Gx n m iii 52. x = 0, n = 0, m = 4
Cl v PPh2 53. x = 1, n = 0, m = 12
Gx Si Gx n Si
n Cl PPh2 54. x = 0, n = 1, m = 4
m m 55. x = 1, n = 1, m = 4
Gx is the generation x of the carbosilane dendimer, e.g. G0 = tetraallylsilane or tetravinylsilane
Scheme 15. Synthesis of diphenylphospine functionalized carbosilane dendrimers, reagents (i)

HSiMe2CH2CI2 [Pt]; (ii) HSiMeCI2, (iii) HSiMeCI2 [Pt], (iv) Ph2PK; (v) Ph2PCH2Li-TEMEDA.
These diphenylphosphine terminated carbosilane dendrimers were used as ligands in the

rhodium catalyzed hydroformylation of 1-octene. The catalyst was prepared in situ by mixing
(acetylacetonato)dicarbonylrhodium(I) and the dendrimeric ligand under H2/CO pressure of
20 bar. Model compounds (H3C)3SiCH2PPh2 (56) and (H3C)2Si.CH2PPh2 (57) were used for
comparison. The selectivity for the linear and branched aldehydes of the dendrimeric systems
is the same as that of the model systems 56 and 57 (Table 6).[69-71] Neither isomerization of
1-octene nor hydrogenation to alkanes and alcohols was observed during the catalytic
reactions. The dendrimeric structure, i.e., the different generations of dendrimers with
monodentate and bidentate end groups, has no influence on the selectivity of the reaction.
However, differences in reaction rates between the various dendrimeric ligands have been
observed. The dendrimers with bidentate end groups (14-16) give slower catalysts than the
dendrimers with monodentate end groups (7-12), a difference that is also observed for the
model compounds (56 and 57).[69-71]
Reetz et al. modified Meijer’s 16-branch polypropylene imine dendrimer with chelating
diphenylphosphine ligands, which led to a 32-branch phosphine dendrimer. This
polyphosphine dendrimer formed complexes with various transition-metal groups such as
PdMe2 or Rh(cod)BF4 (cod=1,5-cyclooctadiene) which had catalytic properties.[72,73]
Hydroformylation of 1-octene with the RhI dendritic catalyst showed a turnover number
comparable to that of the monomer. It was pointed out that such catalysts could be separable
by membrane separation techniques.[72]
Table 6. Results of rhodium catalysed hydroformylation of 1-octene using various

dendrimeric ligandsa.
a
T = 80oC, pco=pH2 =10 bar, [Rh] = 1mM, [1-octene] =638mM in toluene, P/Rh = 2.5, conversion after
1h.
Gong et al. synthesized four water-soluble dendritic phosphonated ligands based on

PAMAM dendrimers of generation 3 (32 end groups) with the hydrophilic amine or sulfonic
acid group on the surface of the dendrimer. For this purpose, the PAMAM dendrimers were
allowed to react with [Ph2P(CH2OH)2]Cl and 1,3-propane sultone. The RhI dendritic
complexes were used as the catalysts in the two-phase hydroformylation of styrene and 1-
octene under mild reaction conditions (40 °C, 20 atm). High catalytic activity for both styrene
and 1-octene and high selectivity for the isoaromatic aldehyde were found.[74]
Cole-Hamilton’s group reported on the synthesis of dendrimers based on polyhedral
oligomeric silsesquioxanes cores with 16 PPh2 arms (Figure 13) that give much higher linear
selectivities (14:1) than their small molecule analogues (3-4:1) in the hydroformylation of
cyclooct-1-ene catalyzed by the RhI complex.[75-77]
In this metallodendrimer, the phosphorus atoms are separated by five atoms including
one silicium atom, i.e., 4-7 Å within one arm, while this distance in the 5-10 Å range between
arms (from molecular modeling). Indeed, analogous metallodendrimers containing only one
more CH2 unit between the Si and P atoms showed no special selectivity enhancement over
the monometallic catalysts. This positive dendritic effect was explained by the steric
crowding and small arm length inducing eight membered ring bidentate coordination that
enhances the linear selectivity. Fluxionality within the complex was also suggested based on
31
P NMR studies.[75-77]
The cooperating groups of Alper, Arya, and Manzer[78,79] prepared a number of Rh-
based supported dendritic catalysts and tested them in the hydroformylation of styrene, vinyl
acetate, vinyl benzoate, and a number of other olefins. On silica, PAMAM dendrimers were
converted into diphosphine ligands and further into Rh complexes (Scheme 16).[78a]
Figure 13. Cole-Hamilitons polyhedral silsesquioxane cores.
O O
H
SiO2 O Si N N NH2 i
N N
O H
O
2 2
PPh2
O O
SiO2 O
H ii
Si N N N PPh2
N N
O H
O 2 2
Ph2
P Rh(CO )Cl
O O 2
H
SiO2 O Si N N N PPh2
N N
O H
O
2 2
(i) HPPh2 and CH2O & (ii) [Rh(CO)2Cl]2
Scheme 16. Preparation of silica-suported dendritic catalysts for hydrofrmyltion.

Initially, only the ligands and complexes of the zero to second generations could
effectively be formed. Because of steric hindrance, the functionalization and complexation of
the third and fourth generations only occurred with extremely low efficiency. The catalysts
demonstrated high activity and strong selectivity toward the branched product. The third-and
fourth-generation catalysts were only marginally active at room temperature, probably
because of the very low metal loading on the silica. Nevertheless, at 75 °C, even these
catalysts were active. Moreover, from the reported turnover rate measurements, it seems that
the activity of the catalyst increased as a function of the generation. Regretfully, this point
cannot be unequivocally concluded because, in this study and in subsequent reports from
these groups, the catalysts were compared with an equal amount of silica/polymer rather than
metal. The apparent turnover frequency is often affected by the initial amount of the catalyst.
The improvement for the third- and fourth-generation catalysts was achieved through the
elongation of the diamine fragment of the branching module of the PAMAM dendron.[79b]
The extension of the branch length, the 1,2-diaminoethane being substituted by 1,4-
diaminobutane, 1,6-diaminohexane, or 1,12-diaminododecane, relieved steric crowding and
presumably led to more dendron-like structures and an increase in the metal catalyst loading.
The length extension indeed resulted in additional improvement in the activity and
recyclability of the catalysts. The best results were achieved for the fourth-generation catalyst
based on diaminododecane, which could be recycled four times without a loss of activity. The
preparation of superior catalysts through changes in the design and generation of the dendritic
template is remarkable, although exact conclusions regarding the change in activity per metal
equivalent, as well as the existence and magnitude of the dendritic effect, cannot be drawn
because the report did not contain critical data about the metal loading on silica.
The same cooperating groups also prepared polyamidodendrons on polystyrene.[78a] The
dendrons incorporating 3,5-diaminobenzoic acid based peptide-like monomers were
decorated with diphosphine chelate ligands and their Rh complexes. The hydroformylation
reaction again demonstrated high activity associated with this type of design of the catalytic
system. The second- and third-generation derived catalysts were more active than the first-
generation-derived one and could be recycled a number of times without a loss of activity.
An additional study explored the influence of the isolation of the catalyst environment on
the polystyrene supported catalytic systems in the hydroformylation reaction was also
investigated. In this study, first- and second-generation dendrons were constructed on
polystyrene, and the biphosphine-rhodium complex was attached to the first-generation
module.[78b] In the second-generation dendrons, the outer layer modules did not carry metal
and were used to isolate the catalytic site from the environment. Although the metal loading
of the second-generation catalyst was lower than that of the first (because the number of
metal atoms per dendron was equivalent for both), the reactivity and recyclability of the
second generation-derived catalyst were notably better with some substrates (e.g., vinyl
benzoate). This interesting dendritic effect again emphasizes the influence of the dendritic
template architecture on the catalytic outcome.
The two aforementioned catalytic systems on polystyrene were further evolved into a
dendritic catalyst with lysine-containing peptide-like modules.[79c] Each monomer thus
formed four propagation sites. First- and second-generation catalysts bearing 4 and 16
rhodium complexes, respectively, on each dendron were formed. These catalytic systems
showed even higher reactivity (enabling room-temperature hydroformylation), excellent
regioselectivity (higher than that of the first two systems, probably because of the lower
reaction temperature), and outstanding recyclability. This catalytic system was successfully
applied to the carbonylative ring expansion of aziridines.
Fan et al. have been reported on the synthesis of a new class of dendrimers functionalized
with triphenylphosphines at the periphery by using convergent method (Figure 14).[80] The
Frechet’s polyether dendrimer instead of poly(propyleneimine) (PPI) or poly(amidoamine)
(PAMAM) dendrimers was chosen as the backbone, which is inert to almost all reactions. All
of the obtained results clearly demonstrated the formation of monodispersed dendrimer
functionalized with phosphines at the periphery. In this study, the rhodium-catalyzed
hydroformylation of olefins was chosen as the model reaction. The catalysts were prepared in
situ by mixing Rh(acac)(CO)2 and the dendritic ligand under a CO/H2 pressure of 20 bar.
Styrene and 1-octene were chosen as the standard substrates.[80]. The results are summarized
in Table 7.
PPh2
OCH 2
Ph2P CH2O
O PPh2
H3CC OCH2 OCH 2
PPh2 O C CH3 H3CC OCH2
3 Ph2P CH2O
OCH
O 2
PPh2
58 3
59
OCH
2
PPh2 3
Figure 14. 60
Figure 14.
Table 7. Hyedroformylation of olefins catalyzed by dendritic Rh (CO)2(PPh3)2 catalystsa.
a
Reactions were carried ot with 0.5m of olefin under the following reaction conditions: substrate/Rh
=500:1; temperature =80oC: 2ml solvent. 20bar(CO/H2 =1).
b
Selectivity of aldehyde was more than 99%.
As shown in Table 7, high reactivity and regioselectivity for the first generation
dendrimer catalyst was observed with low catalyst loading, which was comparable to the
parent catalyst (entries 1 and 2). However, the second and third generation catalysts gave low
regioselectivity and significantly decreased conversion (entries 3 and 4). The profound
generation effect was due to the insolubility of the higher generation catalyst in toluene.
Therefore, dichloromethane was chosen to be the reaction medium in order to sustain
homogeneous reaction conditions for all generation catalysts. In comparison with those in
toluene, high conversion was obtained (entries 7 and 8). The regioselectivity slightly
decreased with increasing generation of the catalysts, albeit higher than that of the parent
catalyst (entries 5-8). In contrast, hydroformylation of 1-octene gave the linear aldehyde as
the main product. With phosphine:rhodium ratio = 10:1, similar regioselectivity was obtained
for the dendritic systems and the parent catalyst (entries 9-12).[80]
Interestingly, after PAMAM dendrimers have been successfully grown in SBA-15
mesoporous materials, Wilkinson’s catalyst (RhCl(PPh3)3) precursor has been tethered on
these dendritic supports to produce heterogeneous catalysts for hydroformylation reaction of
styrene.[81,82] SBA-15 has been functionalized by two methods. In the passivation method,
the silanols outside the SBA-15 pores have been passivated to preclude the rhodium precursor
to be tethered outside the channels. The rhodium catalysts supported in the pore channels of
this passivated SBA-15 show positive dendritic effects in enhancing the catalytic activity,
regio-selectivity and stability of the catalyst by minimizing the leaching of the rhodium
complex catalyst from the catalyst support to the liquid-phase media.[81,82]
6.3. Dialkylzinc Addition to Unsaturated Substrates
6.3.1. Dialkylzinc Addition to Aldehydes

Meijer and Peerlings reported the first catalytic studies with high-generation
dendrimers.[83-85] They studied the increased influence of conformational rigidity as the
generation number increases in poly(propyleneimine) dendrimers on the asymmetric addition
of diethylzinc to benzaldehyde catalyzed by optically active amino alcohols (Scheme 17).
This reaction is indeed an ideal test reaction for the induction of asymmetry by amino alcohol
catalysts.
O 2% Catalyst OH
+ ZnEt2
*
H toluene / hexane
Scheme 17. Diethylzinc addition to benzaldehyde.
Poly(propyleneimine) dendrimers have been modified with (R)-phenyloxirane and their

corresponding N-methylated derivatives (Figure 15), and these dendritic catalysts have been
tested for the addition of diethylzinc to benzaldehyde. The chemical yields and ee drop as the
dendritic generation of the catalyst increases (ee drops from 36% for the monofunctional
catalyst to the fifth-generation dendritic catalyst).[83,85] Optically active R-styrene oxide was
also brought into reaction with the amine-functionalized poly(propyleneimine) dendrimer
yielding mainly the secondary alcohol-secondary amine functionalities. Reaction of
diethylzinc with benzaldehyde using these dendritic catalysts led to a dramatic drop in
enantiomeric excess, going from 11% to 0% for catalysts with 1-64 end groups. Thus, the
dendritic effect is negative in both of these cases. This negative dendritic effect was attributed
to an increase in steric hindrance of the end groups at the periphery of the dendrimer,
resulting in an increased difficulty for all end groups to adopt their preferred conformation in
order to catalyze the diethylzinc addition. The presence of H-bonds greatly enhances this
effect.
Rheiner and Seebach used dendritic Ti-TADDOLates with Fréchet-type branches up to
the fourth generation (64 branches) in the enantioselective addition of Et2Zn to
benzaldehyde.[86] There was no detectable decrease of selectivity (98:2) up to the second
generation, and the rates hardly decreased up to the third generation. Enantiomeric branches
caused no change for stereoselectivity within experimental error. The authors pointed out that
there might be applications for special properties such as high molecular weight, good
solubility, and spacing of central sites from cross-linked polymer matrixes.
Figure 15. Peerlijgs and Meijer’s poly (propylene imine) dendrimers modifield with ®-phenyloxirane
for the catalytic asymmetric addition of diethylzinc to benzaldehyce.
Seebach et al. used Fréchet’s dendrimers with styryl end groups to cross-link a catalyst to
a polystyrene support. The catalyst ligand core, TALDOL, is coordinated to Ti(IV) (Figure
16). It has been used for the enantioselective catalysis of nucleophilic addition of diethylzinc
to aldehydes. High enantioselectivities were obtained for the addition of diethylzinc to
aldehydes. The Ti(IV)-TADDOL dendritic polystyrene catalyst also has a much higher
turnover rate than linear polystyrene analogues.[87,88]
The same authors further extended their studies to such dendritic catalysts with spacers of
variable length and flexibility and found remarkable features: (i) while the enantioselectivity
is above 9:1 with all polymers of low loading, only the dendritic polymer gives rise to a
constant selectivity of 98:2 in 20 sequential applications; (ii) the catalytic performances drop
with increasing the chain length of the spacers between the TADDOL core and polymer
backbone; (iii) the low-loaded dendritic catalyst beads with the shortest spacer keep their
swelling properties high even after 20 runs, while all others do not swell as well after multiple
reuse; (iv) the rate of reaction is the same with and without stirring using the beads of
dendritic catalyst that has the shortest spacer filling the whole reaction volume under standard
conditions. This means that diffusion of reactants and products to and from the active center
is obtained.[89,90] Moreover, the authors investigated the use of membrane reactors in these
enantioselective catalytic reactions. Therefore, they synthesized TADDOL derived dendritic
catalysts with a molecular weight high enough to be retained inside a membrane that is
impermeable to the catalyst but permeable to reactants and products.[91]
Figure 16. Seebach’s denddritic Ti-TADDOLates coordinated with Ti(IV) with Fre’chet-type branches
(homogeneous and heterogeneous on polystyrene support) for the enantioselective addition of
diethylzinc to benzaldehyde.
Seebach and co-workers have been also synthesized a hexa-arm dendrimer and attached
their ligand of C2 symmetry, TADDOL (α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanol)
(Figure 17), and the Ti(OCHMe2) group at the periphery. Using this chiral metallodendrimer,
the authors found that the enantiomeric addition of diethylzinc to benzaldehyde proceeded
with the same enantioselectivity (ee, 97%) as the monomeric chiral catalyst. The
metallodendrimer, with a molecular weight of only 3833 Da, had to be separated by column
chromatography rather than by ultrafiltration methods.[92,93]
Figure 17. Seebach’s hexa-arm dendro,er attached to chiral TADDOL who related metallodendrimer
with Ti(OCHMe2) group at the periphery.
Very interesting rigid dendrimers have been constructed by Pu’s group around an
optically pure diacetate of 4,4′,6,6′-tetrabromo-1,1′-bi-2-naphthol (Figure 18).[94]
The G-2 dendrimer catalyzed the asymmetric alkylation of benzaldehyde with diethylzinc
with a much higher catalytic activity (98.6% conversion in 24 h at room temperature) than
(S)-BINOL (37% conversion under these conditions) and also generates the opposite
enantiomeric product.[94] Both enantioselectivities of the dendrimer and BINOL are very
low. This dramatic difference is due to the fact that the zinc complex formed from the
reaction with BINOL is likely to exist as aggregates in solution through intermolecular Zn-O-
Zn bonds which should greatly reduce the Lewis-acid activity of the zinc center. Such
aggregate is not formed in the case of the dendrimer due to the bulky and rigid dendritic arms,
yet the molecular models show that there is enough space allowing the substrate to approach
the reaction center. High enantioselectivity in the presence of [Ti(O-i-Pr)4] was found for the
dendrimer (100% conversion, 90% ee) as well as for BINOL (100% conversion, 89% ee),
indicating that the catalytic center must be identical, i.e., monomeric, in both cases. The
advantage of the dendrimer over BINOL is that it can be easily removed from the reaction
mixture by precipitation with methanol.[94]
t-Bu t-Bu t-Bu

t-Bu
t-Bu t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu t-Bu
t-Bu t-Bu
t-Bu t-Bu
t-Bu t-Bu t-Bu
Figure 18. Pu’s rigid denderimers constructed around an optically pure diacetate of 4, 4’,6,6’-
tetrabromo-1,1’-bi-2=naphthol.
O O O
n n n
O O O O O
H
O N N
OH OH OH
OH OH OH
H
O N N
O O O O
O
O n n n
O O
64 (n=0-3) 65 (n=0-3) 66 (n=0-3)
Figure 19.
Fan et al. have been reported on the synthesis of two kinds of dendritic chiral BINOL
ligands through the condensation reaction between 2,2'-dihydroxy-1,1'-binaphthyl-3,3'-
dicarboxylic acid and Fréchet-type polyether dendrons with primary and secondary amine at
the focal point, respectively (see Figure 19). The chiral dendritic BINOL ligands 64-66 were
successfully prepared in moderate yields through several chemical transformation
reactions.[95]
Asymmetric induction of the above-mentioned dendritic BINOL ligands in the
enantioselective addition of ZnEt to aldehydes in the presence or in the absence of
2
Ti[OCH(CH ) ] was investigated.[95] For comparison, the corresponding zero generation
3 2 4
compounds 65-G and 66-G were also synthesized. All these dendritic chiral BINOL ligands
0 0
were found to be highly effective and chemoselective in the titanium-catalyzed addition of
diethylzinc to benzaldehyde, which was converted to 1-phenyl-1-propanol in more than 98%
yield and with no byproduct. As shown in Table 8, when using benzaldehyde as substrate, the
size of the dendritic wedges of 65 did not significantly influence the enantioselectivity of the
catalyst (entries 2-5). In order to further demonstrate the size/generation effect of the dendritic
BINOL ligand 65, another two aldehydes were used as substrates. When using ortho-
chlorinated benzaldehyde as substrate, similar enantioselectivities were obtained as compared
with those of benzaldehyde (entries 7-9). In the case of meta-chlorinated benzaldehyde, slight
decrease of ee was observed upon going from the first generation to the third generation
dendrimer (entries 10-12). Upon completion of the reaction, chiral BINOL ligands were
quantitatively precipitated by the addition of methanol and recovered via filtration. The
recovered ligands showed the same enantioselectivity and reactivity (entry 6).[95]
Table 8. Asymmetric addition of diethylzinc to benzaldehyde catalyzed by (R)-Binol

ligands in the presence of Ti[OCH(CH3)2]4a.
a
Benzaldehayde: ligand: ZnEt2 =1.0: 0.2:3 (molar ratio), reaction temperature = oC; solvent = toluene;
reaction time =7hr.
b
Determined by chiral GLC analyses. The absolute confiruration of product is R.
c
Recycle chiral dendritic BINOL ligand was used.
Table 9. Asymmetric addition of diethylzinc to benzaldehyce catalyzed by (R)-BINOL

and dendritic BINOL ligands in the absence of Ti[OCH(CH3)2]4a.
a
Benzaldehyde : ligand : ZnET2 =1.0: 02: 3 (molar ratio), reaction temperature = 0 oC; solvent, toluene;
reaction time = 7hr.
b
Determined by chiral GLC analyses. The absolute configuration of product is R.
The same authors also examined the use of these dendritic BINOL ligands in catalyzing
the enantioselective reaction of benzaldehyde with diethylzinc in the absence of
Ti[OCH(CH ) ] (Table 9).[95] It was found that these chiral dendritic ligands performed
3 2 4
very differently from the BINOL and 64. (R)-65 gave high conversion, albeit much lower
enantioselectivity as compared to 64 (entries 1 and 2). In contrast to (R)-64 and (R)-65, (R)-66
offered the highest enantioselectivity in the asymmetric addition of diethylzinc to
benzaldehyde in the absence of Ti[OCH(CH ) ] (Table 9, entries 3 and 4). This was possibly
3 2 4
due to the formation of better catalyst through the coordination of nitrogen on the linker to
zinc atom. On the other hand, the enantioselectivity decreased upon going from 66-G to 66-
0
G (entries 3 and 4).[95]
1
Recently, new Fréchet-type dendritic BINOL ligands bearing several BINOL units at the
periphery [(R)-67 and (R)-68] have been successfully synthesized (Figure 20). The (dendritic
BINOL) Ti(IV) complexes were proved to be efficient catalysts for the enantioselective
addition of diethylzinc to various kinds of aromatic aldehydes (Table 10). Dichloromethane
was chosen as the reaction solvent, and the molar ratio of BINOL in dendritic ligands to
Ti(O-iPr)4 was 1:10 as the reaction conditions.[96]
Figure 20.
Table 10. Asymmetric addition of diethylzinc to different aldehydes catalyzed by

dendritic BINOL ligands.
As shown in Table 10, using the catalysts derived from these dendritic BINOL ligands,
high yields and good enantioselectivities were achieved for benzaldehyde (entries 1-2), 1-
naphthaldehyde (entries 3-4), m-methoxybenzaldehyde (entries 5-6), and p-halobenzaldehyde
(entries 9-14). As far as o-bromobenzaldehyde was concerned, moderate enantioselectivities
(entries 15-16) with such ligands were obtained. As for p-methoxybenzaldehyde, the
enantioselectivity decreased with the increase of generation (entries 7-8). When (R)-67-G0
and (R)-68-G1 were used, the addition of diethylzinc to benzaldehyde gave high
enantioselectivity to afford the corresponding alcohols with 87.3% ee and 87.1% ee,
respectively.[96]
The recyclability of the dendritic ligand (R)-68-G1 (Figure 20) in the reaction system was
examined. The dendritic ligand (R)-68-G1 was quantitatively precipitated by the addition of
methanol and recovered via filtration. The recovered ligand was reused to the asymmetric
addition of diethylzinc to benzaldehyde. After five times recycles, the yield and
enantioselectivity were hardly reduced.[96]
In an interesting approach, disulfides bearing (R)-1,1’-bi-2-naphthol ((R)-BINOL)
moieties at each terminal position have been successfully introduced on the surface of Au
cluster (Scheme 18). TiBINOLate complex generated from the obtained monolayer-protected
Au cluster (MPC) promoted catalytic asymmetric alkylation of benzaldehyde with Et2Zn
affording the addition product in up to 98% yield with 86% ee. The high catalyst activity of
MPC supported BINOL catalysts would reflect the naked character of BINOL moieties on the
surface of MPC. After completion of the reaction, the BINOL-functionalized MPC was easily
recovered.[97]
Scheme 18.
Soai et al. have been reported on the synthesis of chiral dendrimers with three or six
chiral β-amino alcohol moieties on hyperbranched hydrocarbon chain-ends (Scheme 19). The
enantioselective addition of dialkylzinc to aldehydes was examined using dendrimers 69 (G1)
and 70 (G2) as chiral catalysts (Scheme 18). The results are summarized in Table 11.[98]
In the presence of chiral dendrimer 69-(G1) (3.3 mol%), benzaldehyde (71a) was
isopropylated with i-Pr2Zn to give (R)-2-methyl-1-phenylpropan-1-ol (72a) in high
enantioselectivity (86% ee) (Table 11, entry 1). Furthermore, enantioselective isopropylation
of benzaldehyde and 2-naphthaldehyde catalyzed by higher-generation dendrimer 70-(G2)
yielded 72a and 72b in 80 and 86% ee, respectively (Table 11, entries 7 and 8). The catalysts
69-(G1) and 70-(G2) themselves are soluble in toluene, and were recovered and reused
without any loss of enantioselectivity (Table 11, entries 2 and 3). Thus, the rigid backbones
of 69-(G1) and 70-(G2) are effective at impairing an unfavorable intramolecular interaction
between the catalytic sites.[98]
OH N
N N
OH
OH
N
N
OH
OH
N
N
HO
69-(G1)
Chiral catalyst 69 or 70 R1 R R2 N
HO
N
HO
R1 CHO + R2 2Zn (3.3 mol%)
71a-c R2=i-Pr, Et OH
toluene
72a-c (R2=i-Pr) 70-(G2)
73a-b (R2=Et)
Scheme 19.
Soai et al have been further reported on the synthesis of other structures of chiral
dendrimers bearing also chiral β-amino alcohols on their hyperbranched chain-ends. The
dendritic chiral ligands 76 and 77 bearing four and eight sites of chiral amino alcohols,
respectively, were prepared by attaching ephedrine derivatives at the periphery of
polyamidoamine (PAMAM) (Figure 21). Chiral diamine 74 and diimine 75 possessing
ephedrine moieties were also prepared. These chiral ligands serve as highly enantioselective
catalysts and ligands in the enantioselective addition of dialkylzincs to aldehydes with up to

93% ee.[99]
Table 11. Enantioselective alkylation of various aldehydes using chiral catalyst 69 (G1)
and 70 (G2).
Aldehyde (71) (R)- Alcoholb

a
Entry R 2
Chiral catalyst
R1 Yield (%) ee (%)
1 phenyl 71a i-pr 69-(G1) 72a 63 86

2 Et 69-(G1) 73a 61 78
3 Et 69-(G1)c 73a 64 77
4 2-naphthyl 71b i-pr 69-(G1) 72b 59 84
5d Et 69-(G1) 73b 50 86
6 p-tolyl 71c i-pr 69-(G1) 72c 67 77
7 phenyl 71a i-pr 70-(G2) 72a 70 80
8 2-naphthyl 71b i-pr 70-(G2) 72b 32 86
a
Reaction was perfomed in tulene, 2.2 molar equiv. of dialkylzinc was added to a solution of aldehyde
and 3.3 mol% of chiral catalyst and the mixture was stirrect at room temperature for 15-96h.
b
.ee was determined by HPCL analysis using chiral column. Configuration of 72a and 72c are
tentatively assigned based on that of 72a.
c
Recovered catalyst was used.
d
4.1 molar equiv of diethylzinc was used.
HO N H
N
N
H N HO OH
OH
74 N N
OH NH HN HO
HO N
N N N
N
HN NH
N OH O O
HN NH
75 NH HN
O N N O
O O
HN NH
N N
HN NH
N OH O O
HO N N
O N O
NH HN
NH HN HN O NH
O HN O
O NH
N N N
H NH
N OH HO
N NH HN
HN NH
O O
HN HN
N N
HO N N OH
HO OH
76 77
Figure 21.
The same authors also synthesized chiral dendrimers 79 and 80 bearing four and 12 chiral
ephedrine sites, respectively (Figure 22).[99] Chiral dimer 78 was also prepared. The
carbosilane backbone is more flexible than the poly(phenylethyne) backbone, and the
backbone hardly coordinates to dialkylzinc reagents. These chiral catalysts were employed in
the enantioselective addition of dialkylzincs to aldehydes.[99] The ee reached 93% in the
addition of diisopropylzinc to 3-phenylpropanal. When chiral dendritic catalyst 80 (1.7
mol%) bearing 12 chiral sites was employed, enantiomerically enriched sec-alcohols with 83-
93% ee’s were obtained. The highest, 93% ee, using catalyst 80 was attained in the
enantioselective addition of diisopropylzinc to 3-phenylpropanal. Chiral dendritic catalyst 80
could be recovered and used without any loss of reactivity and enantioselectivity. It should be
noted that the enantioselectivities attained by using chiral dendritic catalysts 79 and 80 are
comparable with those attained by using chiral dimer catalyst 78 (Figure 22).[99]
OH Si
N Si N OH
OH
HO N
N
78 OH
OH N
N
Si Si
Si Si
OH N
Si OH
N Si Si Si
OH
N OH
N Si
OH N
Si Si Si Si
N Si Si HO
Si Si
Si
Si Si
N
Si Si HO N HO
N N
HO N N HO HO
HO
79 80
Figure 22.
Hu et al have been synthesized optically active ephedrine-bearing dendronized polymers

81 and 82 by using the Suzuki coupling polymerization (Figure 23). These polymers were
obtained in high yields. They are soluble in common organic solvents such as THF, toluene,
chloroform and dichloromethane. Gel permeation chromatography (GPC) analysis
(polystyrene standards) shows the molecular weight of 81 is Mw = 141 100, Mn = 50 400
(PDI = 2.80).[100]
The application of ephedrine-bearing dendronized polymers 81 and 82 as
macromolecular chiral catalysts for the asymmetric addition of diethylzinc to benzaldehyde
was investigated and compared the catalytic properties with their corresponding linear
polymeric and dendritic chiral catalysts.[100] The dendronized polymers 81 and 82 were
found to be more efficient than their corresponding linear polymeric. In the presence of 5
mol% of 81 or 82 (based on the polymer repeat unit) in toluene, diethylzinc adds to
benzaldehyde to afford the addition product (R)-1-phenyl-1-propanol in 75% ee and 73% ee,
respectively. Dendronized polymers 81 and 82 could be easily recovered by filtration and
reused. The recovered 81 shows the same reactivity and enantioselectivity (99% conversion
of benzaldehyde after 12 h, 76% ee).[100]
Ph OH
HO Ph Ph OH HO Ph
N
N N N
OR OR OR OR
n n
n n
n
OR n OR OR OR
n n
C C
C C
81. n = 0
82. n = 1 N N N N
R = n-C6H13 HO Ph Ph OH HO Ph Ph OH
Figure 23.
Rhee et al have been reported on the first use of silica supported dendritic chiral
auxiliaries for the enantioselective addition of diethylzinc to benzaldehyde. The dendritic
chiral catalysts that are shown in Figure 24 were prepared via the reactions of various
dendrimers with (1R, 2S)-ephedrine.[101,102]
O O OH
O H
N N N N *
O Si N N N N
H H *
O O O
Silica 2 2 2 2
Figure 24. Silica supported dendritic chiral B-amino alcohols.
Regardless of the catalyst used, the reaction yielded 1-phenyl-1-propanol as the major
product with chemical yields up to 92% and enantioselectivities up to 62% ee. Benzyl alcohol
is formed via the reduction of benzaldehyde by diethylzinc in the absence of catalyst and this
reaction proceeds slowly in a competitive way. The reaction performance is strongly
dependent upon both the number of generations and the amino group content of initiator sites.
In all the cases with dendritic series, the conversion, selectivity, and enantioselectivity
decreased with an increase in the number of generations. In addition, the reaction
performance could be improved to the level of the homogeneous counterpart by increasing
the diethylzinc concentration. Furthermore, the dendritic chiral catalyst could also be recycled
and reused without a significant loss of catalytic activity.[101,102]
El-Shehawy et al have recently described an interesting approach for the synthesis of a
new kind of dendronized polymers with chiral ephedrine incorporation at the polystyrene
hyperbranched chain-ends PS(Ephed)2-PS(Ephed)16 that are shown in Figure 25 with
hydrocarbon backbone chains (i.e., without any heteroatoms either in the polystyrene main
chain or in the dendritic chain-ends). These chiral dendrimers were evaluated as chiral ligands
for the enantioselective diethylzinc addition to a series of aldehydes. According to his design,
the polymer backbone hardly to coordinate with the dialkylzinc reagent and each chiral site of
the dendritic chiral catalyst is anticipated to work independent of other chiral sites.[103]
OH
Ph
Ph
N
Me
Ph
OH
OH Ph OH
Me Me
Me N Me Me
Me N N Me Ph
Ph OH Me
*
Me OH
* Me Ph
OH Me N HO N N
* OH Me
Ph Ph * Me Me *
OH Ph
*
N N Me Ph Me
Me Ph Me Me
Me N OH
Me
Ph N
OH Me
OH N Me Ph Ph
Me Me
Me * *
N Me N OH N OH
Me
Me
n n n n Me
Me OH
N OH N
N Me Me * *
Me N Me Ph
Me Ph
OH OH
Ph Me
Me N N Me
Me Ph Me
* N Me OH
(1R, 2S)-PS(Ephed)2 Ph OH * Me Me
N Me Ph Me
Ph * Ph
OH * OH
Me N N N Me
(1R, 2S)-PS(Ephed)4 * Me Ph HO
Me
* Me OH
Ph OH Me Me
N N
Me
Me N Me Me Ph
(1R, 2S)-PS(Ephed)8a OH
Me
Ph N OH
(1S, 2R)-PS(Ephed)8b OH Ph
Ph Me Ph
OH
Ephed = Ephedrine
(1R, 2S)-PS(Ephed)16
Figure 25. Structures of chain-3nd functionalized polystyrenes having 2, 4, 8 and 16 chiral ephedrine
moieties PS(Ephed).
The enantioselective diethylzinc addition reaction to benzaldehyde using the

macromolecular chiral catalysts PS(Ephed)2-PS(Ephed)16 was first investigated. The results
are summarized in Table 12. The chemical yield as well as the enantioselectivity of the
addition product was increased markedly on using PS(Ephed)8a that having eight ephedrine
moieties (90% and 94% ee, respectively, Table 12, entry 7). The influence of the molar ratios
of the dendritic chiral catalyst was also examined (Table 12). Interestingly, the diethylzinc
addition reaction to benzaldehyde using the recovered dendronized polymer PS(Ephed)8a
afforded the addition product with a comparable result to that of entry 7 (entry 12). It is more
interesting to note that the high enantioselectivity observed in the asymmetric diethylzinc
addition to benzaldehyde using chiral dendrimer PS(Ephed)8a (90% ee, entry 7) was found to
be comparable to that reported for the same reaction using the corresponding monomeric
chiral catalyst (1R,2S)-N-benzylephedrine (92% ee, entry 7) under otherwise identical
reaction conditions.
Table 12. Catalytic enantioselective diethylzinc addition to benzaldehyde using chiral

dendrimers PS(Esped)2-PS(Ephed)16a.
a
All Reactions were performed in toluene at 0oC using 2.2M equiv of diethylzinc.
b
Yields after purification by column Chromatography (hexane/ethyl acetate =4.1).
c
Determined by HPCL analysis on a chiral stationary phase (Chiralcel OD-H).
d
The absolute configureations were assigned by comparing the sign of their specific rotations with
those reported in the literature.
e
Data in parentheses are obtained from the same reaction using (1R, 2S)-N-benzylephedrine.
Table 13. Catalytic enantioselective addition of dialkylzinc reagents to aldehydes using

dendritic chiral PS(Ephed)8a a.
a
All Reactions were performed in toluene at 0oC using 2.2M equiv of diethylzinc and 6 mol% of chiral
dendrimer.
b
Isiolated yields after flash Chromatography.
c
The ee values were determined by HPCL analysis using a chiral stationarly phase.
d
Absolut configurations were determined by comparing the sign of their specific rotations with those
reported in the literature.
The catalytic efficiency of the dendronized chiral catalyst PS(Ephed)8, bearing eight
chiral sites of ephedrine moieties, was further demonstrated in the dialkylzinc addition
reaction to a series of substituted aldehydes and the results are summarized in Table 13. The
obtained results revealed that the dendritic chiral catalyst PS(Ephed)8a promotes the highly
enantioselective addition of dialkylzinc reagents to all aromatic substituted aldehydes.[103]
Interestingly, the enantioselectivity remarkably increases with more reactive substrates
(compare entries 11 vs 7 and 9 and 12 vs 8 and 10, respectively, Table 13). Most importantly,
the diisopropylzinc addition to 3-phenylpropanal proceeded in a highly enantioselective
manner to give the corresponding secondary alcohol, 2-methyl-5-phenyl-3-pentanol with a
high enantioselectivity of 95% ee (entry 13).[103]
6.3.2. Dialkylzinc Addition to Imines

Soai’s and his co-workers have been made high efforts on the modification of PAMAM
dendrimers with ephedrine ligands giving dendritic catalysts for the rarely reported addition
of dialkylzinc to imines.[104-109] Soai et al. have been reported on the first example for the
use of dendrimeric chiral ligands in the enantioselective alkylation of imines. Chiral diamines
74, 76, and 77 as well as diimines 75, 83, and 84 were prepared by loading a chiral ephedrine
moieties on starburst PAMAM dendrimers (see Figures 21 and 26).[105]
HO OH
N N
OH N N HO
N N
HN NH
HO N N OH O O
N N
NH HN
O N N O
N N O
O O O
N HN NH
H NH
N N N
N
HN NH HN NH
O O O O
N N O N N O
NH HN
N O N
OH HN O
HO N N NH
N N
83 OH N N HO
N N
HO OH
84
Figure 26.
These above-mentioned chiral dendrimers were used as chiral ligands for the
enantioselective addition of diethylzinc to N-diphenylphosphinylimines. In the presence of
chiral diimine 75 and diamine 74, N-diphenylphosphinylamine 86a with >90% ee was
obtained. Dendrimeric chiral ligands 76, 77, 83, and 84 afforded 86a with moderate
enantioselectivities. The results are shown in Table 14. Because dialkylzinc hardly adds to N-
alkylimine even in the presence of amino alcohols, the N-alkylimine type chiral ligand 75 was
not alkylated during the ethylation reaction of N-diphenylphosphinylimine 85a. There was
very little difference in the enantioselectivities between the imino type and the corresponding
amino type chiral ligands (75 and 74 & 83 and 76).[105]
Table 14. Enantioselective addition of diethylzinc to N-diphenyl-phosphinylimine 85a

using varios dentic chiral ligands.
H Ph
Ph chiral ligand Ph N
Ph N Ph + Et2Zn P Ph
P toluene, r.t. Et O
O
85a (R)-86a
(R)-86a
Entry Chiral Ligand (mol%) Time (d) Yyield (%) ee ( %)
1 75 50 2 54 92
2 74 50 2 46 92
3 83 50 2 32 43
4 76 50 2 18 40
5 84 50 2 12 39
6 77 25 3 8 30
Molar ratio immine: ET2ZN = 1:6.
Table 15. Enantioselective addition of diethylzinc to N-Diphenylphosphinylimines 85a-d.
Ph H Ph
Ph N Ph + Et2Zn chiral ligand 50 mol%) Ph * N Ph
P P
toluene, r.t. Et O
O
85a-d 86a-d
Imine 85 Product 86
Entry Chiral
Time (d)
R Ligand Yield (%) ee (%)
1 phenyl 85a 75 2 86a 54 92

2 1-naphthyl 85b 75 2 86b 27 74
3 2-naphthyl 85c 75 2 86c 52 90
4 p-tolyl 85d 75 2 86d 54 93
5 phenyl 85a 74 2 86a 46 92
6 1-naphthyl 85b 74 2 86b 11 71
7 2-naphthyl 85c 74 3 86c 41 89
8 p-tolyl 85d 74 2 86d 38 93
9 phenyl 85a 83 2 86a 32 43
10 1-naphthyl 85b 83 3 86b 10 11
11 2-naphthyl 85c 83 3 86c 25 47
12 p-tolyl 85d 83 4 86d 22 56
Molar ratio immine: Et2Zn = 1:6.
The enantioselective ethylation of various N-diphenylphosphinylimines (85a-d) in the

presence of 50 mol% of chiral ligands 75, 74 and 83 (Table 15) was also investigated. Imines
85a,c,d were ethylated to afford the corresponding addition products 86a,c,d with very high
enantioselectivities in the presence of either chiral dendrimers 75 or 74. The
enantioselectivities of the addition products with the para-tolyl substituent using 75 and 76
reached to 93% ee (entries 4 and 8).[105]
In order to attain high enantioselectivity by using a chiral dendritic catalyst and ligand, it
was necessary to avoid unfavorable coordination between the dialkylzinc reagent and the
framework of the dendrimer. Thus, the same authors devised chiral dendrimers 69 and 70
with hydrocarbon [poly(phenylethyne)], i.e., without heteroatoms, with a backbone bearing
three and six chiral ephedrine derivatives at the periphery, respectively (see, Scheme
19).[107,109] Each chiral site of the dendritic catalysts and ligands 69 and 70 is expected to
work independently of other chiral sites because of the relatively rigid phenylethyne and
approximately planar structure of the backbone.
The enantioselective addition of diethylzinc to N-diphenylphosphinylimines using
dendritic chiral ligands 69 and 70 was examined and the results are shown in Table
16.[106,109] Chiral dendrimer 69 (0.34 mol equiv) promotes the highly enantioselective
addition of diethylzinc to N-diphenylphosphinylimines 10 to produce enantiomerically
enriched (R)-N-diphenylphosphinylamines 11 with 71-94% ee in 73-80% yields (entries 1-4).
Chiral dendrimer 70 (0.17 mol. equiv.) of a higher order generation also accelerates the
reaction to give enantiomerically enriched (R)-N-diphenylphosphinylamines 11 with 85-90%
ee in yields of 74-79% (entries 5-7).
Table 16. Enantioselective addition of diethylzinc to various N-

diphenylphosphinylimines using chiral dentritic legands 69 and 70.
a
All Reactions run in toluene at room temperature using 3.0 molar equiv of diethylzinc.
b
Determined by HPCL analysis using a chiral stationary phase.
Chiral dendrimers 78-80 bearing two, four and 12 chiral ephedrine sites, respectively,
(see Figure 22) have been also synthesized and evaluated as chiral ligands in enantioselective
diethylzinc addition to N-diphenylphosphinylimines.[108,109] The carbosilane backbone is
more flexible than the poly(phenylethyne) backbone, and the backbone hardly coordinates to
dialkylzinc reagents. The results are shown in Table 17.
Table 17. Highly enantioselective addition of dialkylzincs to N-

diphenylphosphinylimines using chiral dendritic ligands 79.80 or chiral dimer 78.
a
Reactions was run in toluene at 0oC for 48 h using 3 molar equiv of diethylzinc.
b
Determined by HPCL analysys using a chiral stationary phase.
c
Recovered chiral dendrimer was used.
As shown in Table 17, the enantioselective addition of diethylzinc to N-

diphenylphosphinylimine derived from 2-naphthaldehyde, promoted by chiral carbosilane
dendrimer 79 (0.25 mol equiv), afforded the corresponding (R)-N-diphenylphosphinylimine
with 92% ee (entry 1). Similarly, the addition of diethylzinc to the same imine using the chiral
dendritic ligand of a higher generation 80 (0.13 mol equiv) afforded the corresponding (R)-N-
diphenylphosphinylimine with 92% ee in 70% yield (entry 7). The use of a lesser amount
(0.083 mol. equiv.) of dendritic chiral ligand 80 also produced the imine with 90% ee in 70%
yield (entry 8). Chiral ligand 79 was recovered and reused without any loss of reactivity and
enantioselectivity (entries 1 and 2). Diisopropylzinc could also be used (entries 4 and 11). The
enantioselectivities of chiral dendritic ligands 79 and 80 are comparable with those of chiral
dimer 78.
El-Shehawy et al. have recently described the synthesis and application of a new kind of
dendronized polymers with chiral ephedrine incorporation at the polystyrene hyperbranched
chain-ends PS(Ephed)n as highly effective chiral ligands for the enantioselective diethylzinc
addition to a series of N-diphenylphosphinoyl arylimines (see Figure 25).[110] The
enantioselective diethylzinc addition reaction to N-diphenylphosphinoyl benzaldimine 85a as
a standard substrate using chiral dendrimers PS(Ephed)2-PS(Ephed)16, in toluene at room
temperature for 48 h, was first examined. The obtained results are summarized in Table
18.[110]
Table 18. Enantioselective diethylzinc addition to N-diphenylphospinoyl imine 85a using

chiral dendrimers PS(Ephed)na.
a
All reactions were performed in toluene at room temperature using 3.0 molar equiv of diethylzinc and
equimolar amounts of chiral polymer (based on the total number of ephedrine moieties against the
imine) and imine 85a except for entry 7, which was perfomed using 1.5 molar equiv of chiral
polymer.
b
Refers to the isolated yields wafter flash chromatography (hexane/ethylacetae).
c
Deterermined by HPLC analysis on a chiral column (Chiralpak AD).
d
The absolute configuration was assigned to be R by comparing the retention time on HPCL with those
reported in literatur3e.
e
Values in parenthesis are obtained from the same reaction using 1.0 molar equiv of (1R, 2S)-N-
benzylephedrine as chiral ligand.
f
Values in parenthesis are obtained by using N-vinylbenzylephedrine copolymerized with strene and
divinylbenzene as Chiral ligand.
Under the same reaction conditions, the enantioselectivity of the addition product 86a
obtained by using PS(Ephed)8a (Table 18, entry 5) was higher than that observed in case of
using PS(Ephed)16 (Table 18, entry 6) as chiral ligand. This was probably due to the fact that
the environments of active sites at the polystyrene chain ends of PS(Ephed)8a might have
enough space to work as a chiral ligand, while the active chiral sites of PS(Ephed)16 interfere
either with each others and/or with the polymer backbone chains. Interestingly, on performing
the diethylzinc addition reaction to benzaldimine 85a using each of PS(Ephed)2 and
PS(Ephed)4, but for longer reaction times (Table 18, entries 2 and 4, respectively), the
addition product 86a was obtained in higher yields with slightly higher enantioselectivities.
It is worth to mention that all the dendritic chiral polymers used in this study are soluble
in toluene and worked well as homogeneous chiral ligands during the reaction. Interestingly,
the enantioselectivity observed in the diethylzinc addition reaction to imine 85a using chiral
dendrimer PS(Ephed)8a (90% ee, Table 18, entry 5) was high as those obtained not only by
using (1R,2S)-N-benzylephedrine (92% ee, entry 5) but also by using polystyrene supported
with the same chiral moiety (89% ee, entry 5) as chiral ligand. Chiral polymer PS(Ephed)8b
worked well as chiral polymer PS(Ephed)8a and led smoothly to the desired secondary chiral
amine 85a with almost the same chemical yield and enantioselectivity, but with reversed
stereoselectivity (Table 18, entry 8).
Table 19. Enantioseletive diethylzinc addition to N-diphenylphosphinoy1 arylimines 85

using chiral dendrimer (1R, 2S)=PS(Ephed)8aa
a
All reations were performed in the toluene at room temperature for 48h using 3.0 molar equiv of
diethylzinc and equimolar amounts of chiral polymer (based on the total number of the ephedrine
moieties against immine) and imine 85 except for entry 14, which was performed using 0.5 molar
equiv of chiral polymer.
b
Refers to the isolated yields after flash chromatography (hexane/ethlacetate).
c
Determined by hpcl analysis on a chiral column (Chiralcel OD or Chiralpak AD).
d
The absolute configuration was assigned by comparing the retention time on the HPCL with those
reported in literature.
e
Recovered dendritic chiral polymer was used.
The diethylzinc addition reaction to a series of N-diphenylphosphinoyl arylimines (85), in

the presence of the dendritic chiral ligand PS(Ephed)8a that showed the best result, was
examined and the results are summarized in Table 19.[110] As it was expected, chiral
dendrimer PS(Ephed)8a promotes the highly enantioselective addition of diethylzinc to all
aromatic substituted phosphinoyl imines 85 to afford the corresponding enantiomerically
enriched (R)-N-diphenylphosphinoylamides 86 with yields of 83-93% and enantioselectivities
up to 93% ee (Table 18). It is interesting to note that phosphinoyl imines bearing para-
substituents on their phenyl groups would provide the corresponding N-phosphinoylamides
with relatively higher enantioselectivity than their analogues having ortho- or meta-
substituted phenyl groups.
The chiral polymer was easily and quantitatively recovered by silica gel column
chromatography followed by reprecipitation from its THF solution to a mixture of methanol
and HCl. As shown in Table 19, the diethylzinc addition reaction to imine 85 (Ar=4-Me-
C6H4) using the recovered polymer PS(Ephed)8a afforded the corresponding addition product
(entry 13) without any significant loss in the enantioselectivity as in entry 4. Since the author
have used in this study an equimolar amount of the dendritic chiral polymer PS(Ephed)8a,
based on the total number of the chiral sites at the periphery, against imines, the obtained high
yields and enantioselectivities of the addition products suggested that nearly all of the chiral
sites at the periphery of dendritic ligand PS(Ephed)8a worked effectively.[110]
Figure 27.
6.4. Epoxidation of Alkenes
Suslick and his co-workers have been designed dendritic chloromanganese(III)

porphyrins (Figure 27) for the catalysis of epoxidation of alkenes with
iodosylbenzene.[111,112] The dendritic wedges are first- and second-generation aromatic
polyesters. They provide a confined environment, and the catalyst provides much better
intramolecular and intermolecular regioselectivities than those obtained with unsubstituted
5,10,15,20-tetraphenylporphyrinatomanganese(III) cation. The least hindered double bond of
unconjugated dienes such as 1,4-heptadiene and limonene is epoxidized preferably. Similarly,
in the epoxidation of a mixture of 1-alkene and cyclooctene, the G2 dendritic
metalloporphyrins showed 2- to 3-fold higher selectivity toward 1-alkenes relative to the
nondendritic catalyst. This regioselectivity provided by the dendritic catalyst is by far not as
high, however, as that of the classical picket-fence porphyrin, 5,10,15,20-tetrakis(2′,4′,6′-

triphenylphenylporphyrin).[111,112]
The dendrimers 87-96 with and without peripheral vinyl groups were prepared via several
synthetic procedures (Figure 28).[113] In most cases, the dendrimers were obtained in yields
between 75 and 95% after purification by flash column chromatography, and they were fully
characterized by 1H NMR, 13C NMR, and IR spectroscopy, by MALDI-TOF or Hi-Res-
MALDI spectrometry, and by elemental analysis.
Figure 28.
The manganese complexes of the dendritically substituted Salens were investigated to

check whether the dendritic modification gives rise to any change in the catalytic activity in
solution. Thus, Salens 87, 88, 91, and 92 were loaded with Mn by heating a solution of Salen
and Mn(OAc)2.4H2O for several hours in EtOH/toluene, while air was bubbled through the
reaction mixture, followed by stirring at room temperature for a further 12 h in the presence
of LiCl. The epoxidation reactions were generally run with 20 mol% of Mn-Salen, two
equivalents of m-chloroperbenzoic acid (m-CPBA) as oxidant and five equivalents of 4-
methylmorpholine-N-oxide (NMO) as additive in CH2Cl2 at -20 oC (Scheme 20).[113,114]
The authors have been examined the epoxidation reaction on several phenyl substituted and
the results are collected in Table 20.
0.2 equiv Mn(Cl)-salen R1 O R2

R1 R2 2 equiv m-CPBA
5 equiv NMO R4 R3
R4 R3
97a-f
CH2Cl2, -20 oC
O O O
a b c
O O
d e O
f
Scheme 20. Epoxidation of various olefins mediated by Mn-salens 87, 88, 91 and 92. Mn (C1) in
homogenous solution to give epoxied 97a-f. The corresponding Mn-Salens were prepared according to
literature procedures.
Table 20. Solective and converstions obtained in the expoxidation of various olifins,
mediated by Mn complexed of Salens 87, 88, 91 and 92 in homogenous solutions.
Epoxide 97 Salen Conversion [%]a) er

a 87 87 73:27
a 88 80 83:17
a 91 79 72:28
a 92 82 84:16
b 87 94 76:24
b 88 83 84:16
b 91 92 76:24
c 87 90 53:47
c 88 58 55:45
c 91 80 53:47
d 87 90 96:4
d 88 75 92:8
d 91 83 95:5
d 92 76 89:11
e 87 94 89:11
e 88 97 90:10
e 91 93 91:9
e 92 98 89:11
f 87 12 57:43
f 88 7 52:48
f 91 8 59:41
a
After 30 min, determined by capillary gas chromatography (CGC).
The selectivities and conversions obtained in the epoxidation of styrene (Æ 97a) with
Salens 87 and 91 were comparable to those obtained with the corresponding (and
commercially available) Jacobsen catalyst under identical conditions (er 75:25, conversion
complete after 1 h). In contrast, enantiomerically highly enriched products and high degrees
of conversions were observed with dendritically modified Salens 87, 88, 91, and 92 in the
epoxidation of 1-phenyl cyclohexene (Æ 97d), again comparable with the results obtained
with the simple unsubstituted Jacobsen catalyst.[113,115,116] Also, epoxidation of
dihydronaphthalene (Æ 97e) gave rise to high enantioselectivities, again similar to the results
obtained with unsubstituted Jacobsen catalyst under the same conditions (er 91:9, conversion
complete after 15 minutes), whereas in the case of trans-stilbene (Æ 97f) the enantiomer
ratios were poor. In general, the selectivities obtained in homogeneous solution using Salens
87, 88, 91, and 92 are similar to those reported for the classical Jacobsen catalyst under
comparable conditions.
Neumann et al have been synthesized new metallosilicate catalysts by reacting a silanol
capped dendrimer, Si[CH2CH2Si(CH3)2OH]4 with MCp2Cl2 (M = TiIV, MoVI, WVI and VV)
(Scheme 21). The resulting Si[CH2CH2Si(CH3)2OMCp2Cl]4 compounds were incorporated in
a silica matrix by the sol-gel method.[117]
Scheme 21.
The catalytic activity of the metallosilicates after calcination revealed excellent activity
and selectivity towards epoxidation of alkenes. A preliminary assay to determine catalytic
activity for epoxidation of alkenes with hydrogen peroxide and tert-butylhydroperoxide
(TBHP) was carried out using cyclooctene, a highly reactive alkene, as a probe substrate.
From the results as described in Table 21, it is clear that TBHP is more effective than H2O2
and that Mo–SiO2 > Ti–SiO2 > V–SiO2 > W–SiO2.
Since Mo–SiO2 and Ti–SiO2 were both active and quite stable to reaction conditions
when using anhydrous TBHP as oxidant, these materials were further tested for activity in
epoxidation of a series of alkenes by TBHP (Table 22).[117] As may be expected, reactivity
was clearly a function of the nucleophilicity of the alkene. Thus, the least nucleophilic
terminal alkenes such as 1-octene and 1-decene were least reactive and required higher
reaction temperatures for reasonable yields. Additionally, yields calculated for TBHP were
high. 2-Methyl-2-heptene was more reactive than 2-octene but there was some loss of
selectivity when the former was used as substrate.
Table 21. Expoxidation of cyclooctene catalysed by metallosilicates.a
Conversion (selectivity) (mol%)

Metallosilicate
Oxidant 30% H2O2 Oxidant 6 M TBHP
None 0 2
Ti-SiO2 39 (98) 95 (99)
V-SiO2 12 (94) 81 (95)
Mo-SiO2 46 (99) >99 (99)
W-SiO2 51 (85) 20 (99)
a
Reaction conditions: 1 mmol cyclooctene, 12 mg metallosilicate catalyst (2 mol% M on SiOd), 2
mmol 30% H2O2 + 1 ml methanol of 1 ml 2 M TBHP on n-decane, 60oC, 8h.
Table 22. Expoxidation of alkenes catalyzed by Ti-SiO2 and Mo-SiO2 with ter-
butylhydroperoxide. a
Conversion (selectivity) (mol%)

Substrate
Ti-SiO2 Mo-SiO2
Cyclooctene 95 (99) >99(99)
Cyclohexene 44 (92) 71 (93)
b
1-octene 25 (81) 56 (95)
1-deceneb 17 (76) 61 (95)
2-octene 21 (97) 62 (98)
2-methyl-2-heptene 29 (90) 90 (90)
a
Reaction conditions: 1 mmol substrate, 12 mg metallosilicate catalyst (2 mol% M on SiOd), 1 ml 2M
TBHP in n-decane, 60oC, 8h
b
100oC
Table 23. Epoxidation of alkenols catalyzed by Mo-SiO2 with ter-butylhydroperoxide.a
Substrate Conversion (selectivity) (mol%)
cis-2-hexen-1-ol 74 (96)
trans-2-hexen-1-ol 87 (97)
cis-3-hexen-1-ol 60 (>99)
trans-3-hexen-1-ol 85 (>99)
5-hexen-1-ol 6 (>99)
a
Reaction conditions: 1 mmol substrate, 12mg metallosilicate catalyst (2 mol% Mo on SiOd), 1ml 2M
TBHP in n-decane, 60oC, 8h.
The molybdenum containing silicate Mo–SiO2 was also surveyed for activity in the
epoxidation of alkenols with anhydrous TBHP (Table 23).[117] Rather unusually the allylic
alcohols were only slightly more reactive than the homoallylic alcohols, whereas 5-hexen-1-
ol reacted like a terminal alkene. Selectivity was high; in the case of allylic alcohols 3-4% of
the allylic aldehyde was formed as by-product.
The Kawi group[118] prepared a similar PAMAM on silica template while amino
terminal groups were converted into salicylimines. These salen-imitating ligands were
complexed with Mn(II) and used as catalysts in olefin epoxidation (Scheme 22 and Table
24), a reaction of growing importance in synthetic organic chemistry.[119-121]
O
O O
NH2 OH H
N N
H (i) N O
N N Mn
(ii) Mn(CH3COO)2 N O
NH2 N
N
H H
O O
R Catalyst R
PAMAM-dervatized silica or regular silica
Ph R = H or Ph Ph O
Scheme 22. Preparation of PAMAM-based supported dendritic Mn catalyst for the epoxidation
reaction.
Remarkably, the catalytic activity per Mn equivalent increased dramatically with the
dendron generation. Thus, in the epoxidation of styrene, the yield increased from 20% for
generation 0 to 75% for the fourth-generation catalyst. Even though the Mn loading per gram
of silica was almost equal for the second-, third-, and fourth-generation catalysts, the yield of
the epoxidation of styrene increased more than twofold in this series.[119-121]
Table 24. Epoxidation of styrene with supported dendritic.
Catalyst generation Yield (%)
0 20
1 26
2 36
3 53
4 75
Zhao et al have been established an operationally simple and mild protocol for the
catalytic enantioselective epoxidation of enones using a series of chiral pyrrolidinylmethanol-
based dendritic catalysts and tert-butyl hydroperoxide (TBHP) as an oxidant. The chiral
dendrimers were synthesized as shown in Scheme 23.[122]
Scheme 23.
Table 25. Screening reaction conditios for the epoxidation of 111a a).
O O
O
Cat./ TBHP
110a solvent, rt 111a
Entry Catalyst Solvent Oxidant T (oC) T (h) Yield (%)b ee(%)c (config)d
1 105 Hexane TBHP rt 48 Trace nde ---
2 105 CCl4 TBHP rt 144 60 66 ---
3 104 CCl4 TBHP rt 120 59 41 ---
4 106 CCl4 TBHP rt 144 64 67 ---
5 107 CCl4 TBHP rt 144 73 68 ---
6 108 CCl4 TBHP rt 144 67 69 ---
7 109 CCl4 TBHP rt 144 70 71 ---
8 106 CCl4 TBHP rt 144 85 69 ---
9 107 + 4 Å MS CCl4 TBHP rt 144 86 73 ---
10 109 + 4 Å MS CCl4 TBHP rt 144 84 74 ---
11 109 + 4 Å MS CCl4 TBHP 0 144 80 13 ---
12 108 + 4 Å MS CCl4/hexane = 1:1 TBHP rt 96 65 66 ---
13 108 + 4 Å MS Benzene TBHP rt 96 66 69 ---
14 108 + 4 Å MS CH2Cl2 TBHP rt 144 20 54 ---
15 108 + 4 Å MS CCl4 H2O2 rt 48 0 --- ---
a
Unless otherwise specified, the reaction was carried out with 1.2 equiv of TBHP in the presence of
30mol% of catalyst.
b
.After column chromatography.
c
Enantiomeric excess was determined by the HPCL analysis using chiral Daicel Chiralce OD column.
d
.The absolute configuration was determined to be (2R, 3S) bu comparison of the HPCL Cretention
time with know data.
e
.Not determined.
A preliminary study was performed to test the catalytic property of these reagents in the
asymmetric organocatalytic epoxidation of enones 13a with TBHP (Table 25). In general,
good conversion of enone 110a was achieved, and the corresponding optically active epoxide
111a was obtained in good yields. The enantioselectivities were moderate to good (41-71%),
with the (2R,3S)-configured product 111a was formed predominantly (Table 25, entries 2-7).
Among all the dendritic chiral catalysts evaluated in this reaction, the second-generation
ligand 109 was the best one in terms of yield and ee (Table 25, entry 7).[122]
To demonstrate the scope and potential for the organocatalytic epoxidation, a series of
different substituted enones 110 were reacted with TBHP at room temperature in the presence
of dendritic chiral ligand 109 (30 mol %) as the catalyst. The results are summarized in Table
26. As shown, almost all reactions proceeded in reasonable reaction times when 30 mol % of
109 was used at room temperature and diastereoisomerically pure trans-(2R,3S)-epoxides 111
were obtained. Different types of electronic substitution on the phenyl ring of the carbonyl
group furnished results comparable to those achieved in the epoxidation of 110 (Table 26,
entries 2-5). It was found that enones with para electron-withdrawing substituents in the β-
phenyl group were all converted to the corresponding optically active epoxides in good yields
and enantioselectivities (Table 26, entries 6 and 7). However, under the same reaction
conditions, an electron-donating substituent did not react with TBHP, due to its low reactivity
(Table 26, entry 8).[122]
Tabke 26. Catalytic enantioselective epoxidation of enones promoted by dentritic lignad

109 and TBHPa.
a
Unless otherwise specified the reaction was carried out with 1.2 equiv of TBHP in the presence of 30
mol% catalyst 109.
b
After colomn chromatography.
c
Enantiomeric excess was determined by the HPLC analysis by using the chiral column.
d
The Absolute configureation was determined to be (2R.3S) by comparison of the HPCL retention
times with known data.
e
Using xx-diphenyl-L-prrrolidinemethanol as the bifuncion organocatalyst.
f
50 mol % catalyst was used in this reaction.
g
Not determined
The recyclability of these catalysts was examined. After the completion of the reaction,
dry methanol was added to the reaction mixture, and the dendritic catalyst 109 was almost
quantitatively precipitated and recovered via filtration. The recovered dendritic catalyst 109
was reused at least five times with little or no loss of activity and enantioselectivity (Table
27).[122]
Table 27. Recylcing use of dendritc catalyst 109 in asymmetric exposidation of chalcone
110 a.
Entry Catalyst T (h) Yield (%)b ee (%)c
1 109 144 84 74
2 109 (second) 144 84 73
3 109 (third) 144 80 72
4 109 (fourth) 144 81 73
5 109 (fifth) 144 83 72
a
Unless otherwise specified the reaction was carried out with 1.2 equiv of TBHP in the presence of 30
mol% of catalyst.
b
After column chromatography.
c
Enantiomeric excess was determined by the HPLC analysis using a chiral Daicel Chiralcel OD
column.
6.5. Palladium-Catalyzed Asymmetric Reactions
Palladium catalysts are one of the most frequently used catalysts in organic synthesis.
There is a large body of literature on palladodendrimer-catalyzed reactions during the last
decade whereby the molecular palladium complex is covalently or supramolecularly attached
to the dendrimer (including silica- or polymer-supported dendrons).[1m,123,124] This whole
area has been recently reviewed in excellent and comprehensive reports by the groups of
Newkome[125] and de Jesús[126] with catalyzed reactions including alkene hydrogenation,
hydrovinylation, polymerization, and copolymerization, carbon-carbon coupling (Stille,
Suzuki-Miyaura, Sonogashira), allylic substitution, aldol-type condensation with
isocyanoacetates, and Michael addition. As with other catalysts, the most important problems
are the cost related to the catalyst efficiency including turnover number of the catalyst (TON),
turnover frequency (TOF), and removal of the catalyst from the reaction mixtures for both
economic (catalyst recycling) and ecological reasons (prevent pollution of the reaction
product by the catalyst).[127-129] Chemoselectivity, regioselectivity, stereoselectivity,
enantioselectivity, and diastereoselectivity, optimized with homogeneous catalysts, are the
other key issues.[130]
van Leeuwen is one of the pioneers of the field of dendrimer catalysis. When he was at
Shell, his group reported a star-shaped hexaphosphine-palladium catalyst with a benzene core
for polyketone formation from alternating CO/alkene polymerization. While the
monometallic catalyst gave 50% fouling (precipitation of the polymer on the wall of the
reactor), this star-shaped catalyst gave only 3% fouling, possibly for solubility reasons. This
is also a very early dendritic effect.[69,131,132] The van Leeuwen group synthesized a series
of diphosphine ligands centered on 1,1′-bis-diphenylphosphinoferrocene bearing dendritic
carbosilane substituents at the para aryl positions in a divergent manner (Figure 29).[132b]
Figure 29. van Leeuwsen’s diphospine lignads centered on 1.1’-bis-diphenylphosphinoferrocene

bearing dendritic carbosilane subsituents at the para aryl positions whose palladium complexes catalyze
allyic alkylations.
Reactions with [Pd(MeCN)2Cl2] afforded the ferrocene-centered chelate complexes, and

these metallodendrimers were shown to be efficient in palladium-catalyzed allylic alkylation
(Scheme 24). The linear trans-product was mainly obtained. The rate of the reaction
decreased, however, as the dendritic generation increased. This negative dendritic effect was
attributed to the more difficult mass transport with increasing the steric bulk of the dendritic
wedges and was more pronounced when going from generation 2 to 3. Remarkably, the size
of the metallodendrimer also determined the selectivity of the allylic alkylation reaction,
because the dendritic bulk hindered the attack of the nucleophile on the Pd-allyl moiety.
Steric interactions between the branches and increase of the P-Pd-P bite angle preferentially
lead to the linear product.[132b]
cata. Ph
Ph
Cl
Ph
( Pd + L
2
+ EtO OEt EtO OEt + EtO OEt
O L= dendritic diphosphine
O O O O O O
Scheme 24.
Scheme 25. Synthesis of chiral dendrimers 114-G3.
van Leeuwen’s group has also synthesized functionalized carbosilane dendrimers. Their
palladium complexes have been used as catalysts in the allylic alkylation performed in a
continuous membrane reactor.[132c] The second-generation carbosilane dendrimer served as
a starting point. It is a white solid whose X-ray crystal structure could be determined and
whose molecular volume of 2414 Å3 was anticipated to be large enough for separation of the
catalyst from the reaction mixture by nanofiltration. The phosphine-functionalized dendrimers
of generation 0, 1, and 2 were synthesized by hydrosilylation of double bonds with
chlorodimethylsilane or dichloromethylsilane followed by reaction with Ph2PCH2-
Li/TMEDA. The dendritic phosphine of higher generation such as that with 72 phosphines
could not be prepared because of steric congestion. The phosphine dendrimers were allowed
to react with [PdCl-(η3-C3H7)]2 yielding either bidendate palladium phosphine dendrimers or
mixtures when monodentate dendritic phosphines were used as ligands. All the
metallodendrimers were used as catalysts in the allylic alkylation of allyl trifluoroacetate and
sodium diethyl methylmalonate yielding diethyl allylmethylmalonate. The reaction was first
carried out in a batch process, and all the metallodendrimers showed a very high catalytic
activity. Using 0.2% of catalyst, the yield was larger than 80% after 30 min and only small
differences of reaction rates were observed for the different catalysts. In a continuous process
using a membrane reactor, the metallodendrimer containing 12 chelated palladium atoms with
a calculated volume of about 7600 Å3 was used as the catalyst. The retention of this catalyst
in the membrane reactor was determined to be 98.1%, which corresponds to a calculated
value of only 25% of decreased activity after flushing the reactor 15 times. Samples taken
from the flow were not catalytically active, which confirms that the observed decrease of
activity was due to decomposition of the palladium complex and not to loss of the dendritic
catalyst.[132c]
Majoral et al. have been reported on the synthesis of a third generation phosphorus-
containing dendrimer possessing 24 chiral iminophosphine end groups derived from (2S)-2-
amino-1-(diphenylphosphinyl)-3-methylbutane. The reaction proceeded gently overnight at
room temperature to yield the chiral dendrimer 3-G3 isolated in 88% yield after work up as a
white powder, very sensitive to oxidation (Scheme 25).[133]
In situ complexation of this dendrimer by [Pd(η3-C3H5)Cl]2 affords a catalyst, which is
used in asymmetric allylic alkylations of rac-(E)-diphenyl-2-propenyl acetate and pivalate.
The percentage of conversion, the yield of isolated 2-(1,3-diphenylallyl)-malonic acid
dimethyl ester, and its enantiomeric excess have been measured in each case, and were found
to be good to very good (ee from 90% to 95%). Furthermore, the dendritic catalyst could be
recovered and reused at least two times, with almost the same efficiency.[133]
Majoral et al reported on the synthesis of chiral ferrocenyl phosphine-thioether ligands
covalently bound on the periphery of 4 phosphorus dendrimers (generations 1-4) having a
cyclotriphosphazene core and on one model compound.[134] The chiral dendrimer were
obtained in nearly quantitative yield after work up. These dendrimers proved to be efficient
ligands for the palladium-catalyzed asymmetric allylic substitution reaction of
dimethylmalonate under classical conditions. The reaction times for completion were almost
the same for the dendrimers of different sizes and the corresponding monomeric ligand.[134]
In every case, isolated yields of the allylated products were very high and enantioselectivities
very close to the one observed for the corresponding monomeric analogue (ee up to 93%).
The reuse of the dendritic catalysts has been carried out simply by precipitation with pentane
at the end of the catalytic reaction. Indeed, these organometallic dendrimers were found to be
efficient soluble polymer-supported catalysts.
Heck olefin arylation, one of the most widely used reactions in synthetic organic
chemistry, was successfully accomplished in solution with aryl iodides, bromides, and even
chlorides, using a variety of catalytic systems.[1d,124,135-137] Heterogeneous catalysis,
however, was performed almost entirely with iodides or electron-deficient
bromides,[138,139] mainly using metal palladium adsorbed on an inorganic support.[140]
The uses of the Heck reaction encompass a vast spectrum of applications, from the synthesis
of fine chemicals, drugs, and natural products to the preparation of novel materials and
supramolecular devices, and include intermolecular and intramolecular versions as well as
asymmetric variants.[1m,124]
The biphosphine-terminated PAMAM-on-silica system prepared from ethylenediamine
(see Scheme 16) was complexed to a dimethylpalladium fragment with (TMEDA)PdMe2 as a
precursor. Before this study, similar soluble systems were prepared and studied by Reetz and
coworkers.[137] As for Rh complexation, the poor functionalization of the third- and fourth-
generation-derived supported catalysts prevented their conclusive investigation. The zero-
generation to second-generation supported catalysts demonstrated activity comparable to that

of the homogeneous analogue in the Heck reaction of bromobenzene (Scheme 26).
P Me
Pd
Y NaOAc, P Me
X R + R
DMF, 48 h, 120 oC Y
PAMAM-derivatized silica or regular silica
Scheme 26. Heck reaction catalyzed by PAMAM-based support catalysts.
Figure 30. Bidente third-generation DAD phosphinated Pd dendrimer for Sonogashira and Suzuki
copling reactions.
Jayaraman compared three generations of Pd-alkylphosphine dendrimers in the Heck

reactions with various olefins and reported that the second and third generations were found
to exhibit better catalytic activity than the monomer and first-generation
metallodendrimers.[141] This trend was also noted by Mapolie with
poly(propyleneime)iminopropylpalladium [142]. On the other hand, three generations of
bidentate DAB phosphinated Pd dendrimers that were found to be active in Sonogashira
coupling of iodo- and bromobenzene with phenylacetylene showed a negative dendritic effect
attributed to increasing steric effect as the generation increases (example for iodobenzene at
25 ◦C, time for quantitative conversion: model: 30 min; first-generation: 15 h; second-
generation: 40 h; third-generation: 48 h) (Figure 30). These metallodendrimers can be
recovered and recycled with little decrease of efficiency up to seven cycles with bis-
cyclohexylaminoalkylephosphine ligands (conversion is 39% after 7 cycles for the third-

generation catalyst). The nature of the alkyl substituents (cyclohexyl versus tert-butyl) on the
P ligand of the Pd catalyst also plays a role in efficiency, solubility and thus recycling
ability.[143-145]
A number of other Pd-catalyzed processes were examined with supported dendritic
systems. The Suzuki reaction was found to be less sensitive to the nature of the dendritic
backbone. The groups of Alper, Arya, and Manzer used the phosphinated PAMAM–silica
constructs to immobilize a variety of Pd complexes. The formed structures were extensively
studied and tested as heterogeneous catalysts in the iodoarene carbonylation reaction
(Scheme 27).[146] Quantitative complexation was observed with zero-generation-to-second-
generation-derived ligands for the PdCl2 fragment. However, for higher generations and with
bulkier Pd fragments, only partial functionalization was achieved. The catalytic reaction was
optimized, and quantitative conversions were readily obtained. With respect to the influence
of the dendritic template structure on the reaction outcome, two trends were observed. First,
higher generation-derived catalysts were characterized by lower Pd loadings and lower
conversions per silica weight unit. However, when the reactivities per Pd equivalent (or
TON/TOF as presented in this article) were compared, they were found to increase with the
generation (Table 28). Second, the leaching of Pd from the support decreased upon an
increase in the dendrimer generation. It is possible that some of the displayed activity resulted
from Pd(0) nanoclusters immobilized inside the silica/dendritic matrix because blackening of
the silica was usually observed under these reaction conditions and no reactivity with
bromobenzene was observed (Pd metal catalysts are usually only reactive toward iodides,
whereas palladium–phosphine complexes are expected to catalyze reactions of both
iodobenzene and bromobenzene). Regardless of the true nature of the catalyst in the
methoxycarbonylation reaction, the demonstrated dendritic effects were quite remarkable.
P X
Pd O
P X
I C
R R OMe

(R= H; 4-NO2; 4-Me; 2-MeO; 4-MeO, 4-CF3; 4-I; 4-Br; 4-OH; 4-CH3CO; 4-I-C6H4)
Scheme 27. Carbonylation reaction catalyzed by PAMAM-based support catalysts the reagents and
conditions are as follows: NET3, MeOH and CO.
Table 28. Methoxycarbonylation of Iodobenzene with Support Dentritic Catalysts.

The Alper group[147] reported also on a Pd catalyzed transformation, hydroesterification

of olefins (Scheme 28), based on C6-spacer-containing PAMAM dendritic catalysts
supported on silica. Because of the longer diamine used in the PAMAM dendron
construction, the phosphine–palladium catalyst could be prepared on up to fourth-generation
dendrons. All the catalysts demonstrated high activity, a preference for the linear product, and
moderate recyclability.
P X
Pd
P X R1
R1 + R2OH + CO 1 CO2R2 +
R
CO2R2
(Reagents and conditions: nonpolar solvent, 150 psi, and 115 oC)
Scheme 28. Hydroesterification reaction catalyzed by PAMAM-based support catalysts.
Moreover, silica-supported polyamidoamine (PAMAM) dendrimers with different spacer

lengths were prepared.[148] After the introduction of diphenylphosphino groups,
complexation to dibenzylidenepalladium(0) gave the desired silica-supported dendrimer-
palladium catalyst complexes G0 to G4-C2-Pd (Figure 31). These catalysts showed activity
towards the oxidation of terminal alkenes to methyl ketones. A dependence of catalytic
activity on the spacer length of the diamine in PAMAM was observed. The authors have
examined the catalytic activity of these dendrimer-Pd complexes towards the oxidation of
terminal alkenes to methyl ketones using tert-butyl hydroperoxide as oxidant.[148]
Figure 31. Dendritic catalysts.
Initially the authors have attempted to oxidize terminal alkenes to methyl ketones under
Wacker-type conditions using the catalysts G0 to G4-C2-Pd. Attempts to optimize the
Wacker-type conditions using Pd complexes of silica-supported PAMAM dendrimers, as
catalysts were unfruitful. Consequently, the oxidant was changed to tert-butyl hydroperoxide.
As a benchmark, the catalytic performance of G0 was investigated using different alkenes.
The addition of organic solvents inhibited the oxidation reaction, and thus the reactions were
carried out under neat conditions. Cyclohexene gave the lowest yield not surprising because
internal alkenes are usually less reactive than terminal alkenes (Table 29, entry 1). 1-Octene
gave higher product yields than 1-decene and 1-tetradecene (Table 29, entries 2-4).[148]
Table 29. Oxidation of various alkenes using TBHP as oxidant.
Catalyst Go-Pd (dba), the Pd content in the reaction mixture was 0.5 mol% substrate (1.50 mmol).
TBHP (1.65 mmol).
55o , C. 24h.
[a]
Yield by GC.
The catalytic activity also proved to be a function of the dendrimer backbone. The higher
generations were less active when screened using 1-octene. Only the first-generation
dendrimer complex gave the methyl ketone in reasonable yield (Table 30, entry 2). The
second and third-generation dendrimer complexes gave poor yields (Table 30, entries 3 and
4). This poor activity was attributed to steric congestion of the dendrimer. This leads to the
threshold for dendrimer growth being reached. Extending the chain length of the diamine
used during dendrimer synthesis can bring relief to steric crowding.[148]
Table 30. The effect of dendrimer generation.
Catalyst Gn-Pd(dba). The Pd content in the reaction mixture was 0.5 mol%. 1-octene (1.50 mmol).
TBHP (1.65 mmol).
[a]
Yield by GC.
The various silica-supported PAMAM-Pd catalysts displayed comparable activity

towards the oxidation of 1-hexene. Extending the olefin length by two methylene groups
starting from 1-hexene to 1-tetradecene gave different results. The different catalysts started
to show different activities. The monomeric catalyst and 1st generation C6 and C12 catalysts
once again gave comparable results. G2-C6 gave the highest conversion of 1-octene while G2-
C12 gave the lowest. A similar trend was observed for 1-decene. In the oxidation of 1-
tetradecene, the G0 and G2-C6 catalysts gave good yields while G2-C12 gave lower
yields.[148] These catalysts could be recycled. The G0 catalyst can be reused up to eight
times giving good yields of 2-octanone. Meanwhile, G1 and G2 complexes can be reused four
times. This catalytic system could be applied to other substituted alkenes. 4-Methyl-1-pentene
could be oxidized in comparable yield to 1-hexene. Good yields were obtained for the
oxidation of 4-phenyl-1-butene. Interestingly, the longer chain diene, 1,8-nonadiene, was only
oxidized at one double bond while 1,5-hexadiene gave a dimerization product in addition to
single double bond oxidation. For terminal olefins with internal bonds like 5-vinyl-2-
norbornene, only the terminal double bond was oxidized.
7. CONCLUDING REMARKS
The use of soluble polymers provides an alternative platform for organic synthesis by
incorporating beneficial aspects of both solution-phase and solid-phase chemistry. By
establishing homogeneous reaction conditions while still facilitating product separation,
soluble polymer-supported methodologies have demonstrated utility in a variety of areas
including peptide synthesis, small-molecule organic synthesis, polymer-supported reagents,
and polymer-supported catalysts. Although great strides have been made in the use of soluble
polymers as supports for recoverable reagents and catalysts, considerable research remains to
be done. It has been recognized that the nature of the macromolecular support plays a
significant role in solid-phase organic synthesis. Compatibility problems between reagent or
substrate and the polymer support can greatly limit the applications of a given support. To
overcome these limitations, soluble polymer-supported reagents and catalysts have been
utilized. Furthermore, in the case of substrates that possess limited solubility, covalent
attachment to a soluble support would allow their use in a previously inaccessible range of
synthetic applications. The refinement of current liquid-phase methodologies coupled with
the development of new soluble polymeric supports tailored for organic synthesis combine to
make soluble polymers an increasingly valuable tool for synthetic chemists.
Over the past three decades, dendrimers have evolved from a concept to become a new
class of polymers with a unique architecture and versatile chemical structures. Progress in
controlled polymerization and synthesis techniques have led to the development of well-
controlled dendrimers structures with a large number of surface groups that can be utilized to
display a wide range of applications. Today, research on dendrimers is not only focused on
disclosing aberrant or special features of dendrimers but considerable effort is also invested in
the development of applications for dendrimers. Some studies in these fields have definitely
shown that dendrimers have beneficial or even superior characteristics, although it should be
noted that frequently more simple monomeric or polymeric systems are equally effective with
respect to the investigated application. There is much more than the aesthetic attraction in the
use of dendrimers in the field of catalysis. The perfect definition of catalytic sites and the
clear possibility to recover the dendritic catalysts have been fully demonstrated. Seminal
studies by van Leeuwen and Brunner’s dendrizyme concept opened the field of dendrimer
catalysis, and then Reetz introduced recycling. The precision of the dendrimer structures, the
specificity of their topology, and the variety of dendrimer generations provides a unique
means to improve catalyst supports. Catalytic efficiency is very often marred by steric
congestion at the metallodendritic surface. Steric congestion may sometimes result in positive
dendritic effects in terms of selectivity. With peripheral catalyst loading, the multiple sites
provide an exceptional density of catalysts, but steric constraints limit the access to the
catalytic centers as shown by several of our examples. The design of star-shaped catalysts or
first generation dendrimers, however, provided catalysts that were as efficient as mononuclear
catalysts and could be recovered and reused, contrary to mononuclear catalysts. Many efforts
have recently concentrated on the recovery of the dendritic catalysts using membrane
reactors. Industrial applications with membrane reactors remain to be carried out, however,
and this aspect is now becoming a major challenge. In some particular cases, interesting
positive dendritic effects in catalysis have been shown by several authors. In most cases,
however, what is hoped for is an efficiency in terms of turnover rates, yields, and
stereoselectivities which is very close to that of the parent, nondendritic analogous catalysts.
Many dendritic effects in catalysis have been observed, including increased/decreased
activity, selectivity, and stability. It is clear from the contributions of many groups that
dendrimers are suitable supports to prepare recyclable transition metal catalysts. Several
separation techniques are applicable to these functionalized dendrimers including
precipitation, two-phase catalysis, and immobilization of the dendrimer to insoluble support
(polystyrene, silica). In addition, the large size and the globular structure of the dendrimers
enable efficient separation by nanofiltration techniques. Nanofiltration can be performed
batch-wise and in a continuous-flow membrane reactor (CFMR). The common problems
involved in catalyst recycling also pertain to dendritic catalysts. These include dendrimer or
catalyst decomposition, dendrimer leaching, metal leaching, and catalyst deactivation.
Although dendritic catalysts have been applied in several reactions, more experiments are
required to gain deeper insight in dendritic effects in catalysis and catalyst recycling. Since
there is no single solution to the catalyst separation problem it is not expected that dendrimers
will provide the general solution. The optimal process clearly depends on catalyst properties
as stability, solubility, etc., as well as product properties. In the development of new
recyclable catalysts systems based on dendrimers, the function of the dendritic part should be
questioned.
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Chapter 10
RECENT STRATEGIES IN PHASE TRANSFER

CATALYSIS AND ITS APPLICATION
IN ORGANIC REACTIONS
P.A.Vivekanand and Maw-Ling Wang*

Hungkuang University, Taiwan, Republic of China.
ABSTRACT
In view of the increasing environmental and economical concerns, it is now
possible. Successful completion of reactions involving lipophilic and hydrophilic
reactants can be achieved by employing an environmentally benign technology viz.,
‘‘phase transfer catalysis’’ (PTC). Some of the prominent features of the PTC include,
improved reaction rates, lower reaction temperatures and the absence of expensive
anhydrous or aprotic solvents. Owing to its simplicity and the low cost of most of the
phase transfer catalysts, the PTC technology has found universal adoption. As a result,
PTC is considered to have great potential for industrial-scale application. Nowadays, due
to these salient features, it has become an important choice in organic synthesis and is
widely applied in the manufacturing processes of specialty chemicals, such as drugs,
pharmaceuticals, dyes, perfumes, additives for lubricants, pesticides, monomers etc. Due
to ever increasing necessity of increasing the efficiency of PTC in industries, researchers
incessantly invented new and novel phase transfer catalysts with more active-sites and
higher efficiency. Asymmetric phase-transfer catalysis has attracted considerable
attention as a convenient technique for the synthesis of chiral molecules. Cinchona
alkaloids and ephedrine derived catalysts are the most popular chiral PTC that has been
employed to achieve the goal for inducing asymmetry into product molecules. Currently,
ingenious new analytical and process experimental techniques viz., ultrasound and
microwave irradiation assisted PTC transformations have become immensely popular in
promoting various organic reactions. Phase transfer catalysis will be of curiosity to
* Corresponding author: Department of Environmental Engineering, Safety and Health, Hungkuang University,
Shalu, Taichung County, 43302 Taiwan, Republic of China. Tel: +886-4-2631-8652 ext.4175. Fax: +886-4-
2652-9226. E-mail: chmmlw@sunrise.hk.edu.tw.
326 P.A.Vivekanand and Maw-Ling Wang
anyone working in academia and industry that needs an up-to-date critical analysis and
summary of catalysis research and applications. In view of the success and vitality of this
technique, we have proposed to present recent happenings in the field of PTC and to
study its applications to various organic reactions. Typical applications of PTC in silent,
ultrasonic and microwave conditions are described. Further, kinetics of various organic
reactions catalyzed by PTC carried out under a wide range of experimental conditions
will be presented.
INTRODUCTION
In recent years, the greening of global chemical processes has become a foremost topic in
the universe. The development of new synthetic methods that are
more environmentally benign have been propelled by the growing importance of green
chemistry in organic synthesis [1]. In general, green chemistry is the only way forwards: it
merges expertise from physical, synthetic and biological chemists, together with that of, life
scientists, environmentalist toxicologists, to deliver sustainable chemical design. Green
chemistry [2], by the design of environmentally compatible chemical reactions, offers the
tools to approach pollution and sustainability concerns at the source. Generally, chemical
transformations, which produce in addition to the desired product large amounts of
byproducts and waste, are less desirable. However by proficient design of chemical
transformations we can reduce the required energy input in terms of mechanical, thermal, and
other energy inputs, and the associated environmental impacts of excessive energy usage. The
necessity of selective transformations in agrochemical and pharmaceutical industries is even
larger since delicate bioactive compounds are often not robust enough to stand the conditions
used in bulk chemistry.
Catalysts aided selective transformations eliminate the requirement of stoichiometric
auxiliary reagents and can eventually help to decrease the amounts of waste. In addition, they
are able to carry out the necessary synthetic transformation in a more environmentally benign
way. Thus, in view of the increasing environmental and economical concerns, it is now
possible.
Transformations of starting materials into desired final products of practical applications
such as pharmaceuticals, plant protection agents, dyes, photographic chemicals, monomers
etc., usually require a number of chemical operations in which additional reagents, catalysts,
solvents, etc. are used. For successful completion of a reaction it is necessary that the
reactants collide with each other as much as possible. However it is often noticed that these
reactions are immiscible in nature. To alleviate the predicament of immiscibility it is
necessary to ferry water soluble anionic reactant into organic soluble reactant/organic phase.
Classical methods [3] to overcome this immiscibility include use of protic/aprotic solvents,
high stirring speed, high temperature etc. Nevertheless these methods have their own
shortcomings viz., high energy consumption, production of byproducts and difficulty in
purification together with environmental pollution. As a consequence, these techniques are
industrially unattractive, constrained and polluting. However, successful completion of
reactions involving lipophilic and hydrophilic reactants can be achieved by employing an
environmentally benign technology viz., ‘‘phase transfer catalysis’’ (PTC).
Recent Strategies in Phase Transfer Catalysis and its Application … 327
GENESIS OF PHASE TRANSFER CATALYSIS

This key green approach [4], leading to waste minimization, utilizes water as the solvent
and is applicable to a great variety of reactions in which inorganic and organic anions and
also carbenes react with organic substrates. It makes use of heterogeneous two-phase
systems-one phase (water) being a reservoir of reacting anions or base for generation of
organic anions, whereas organic reactants and catalysts are located in the second, organic
phase. The reacting anions are continuously introduced into the organic phase in the form of
lipophilic ion-pairs with lipophilic cations supplied by the catalyst. Starks et al.[5] reported
that nucleophilic aliphatic substitution reaction of an aqueous sodium solution with 1-
chlorooctane does not ordinarily take place because of immiscibility. By the addition of 1%
of the quaternary ammonium, hexadecyl tributyl phosphonium bromide, cyanide ions are
ferried into the organic phase from the water phase and 1-cyanooctane formed quantitatively
in a matter of minutes. Some of the prominent features of the PTC include, improved reaction
rates, lower reaction temperatures and the absence of expensive anhydrous or aprotic
solvents.
Emergence of the Methodology
Owing to its simplicity and the low cost of most of the phase transfer catalysts, the PTC
technology has found universal adoption. As a result, PTC is considered to have great
potential for industrial-scale application. Nowadays, PTC becomes an important choice in
organic synthesis [6] and is widely applied in the manufacturing processes of specialty
chemicals, such as pharmaceuticals, dyes, perfumes, additives for lubricants, pesticides, and
monomers for polymer synthesis. Frequently employed PTC are presented in Table 1 and is a
very effective tool in many types of reactions, e.g., alkylation, oxidation, reduction, addition,
hydrolysis, etherification, esterification, carbene addition, chiral reactions etc.
Due to ever increasing necessity of increasing the efficiency of PTC in industries,
researchers incessantly invented new and novel phase transfer catalysts with more active-sites
[7-13] and higher efficiency. Escalating demand for homochiral commercial products in
preference to their racemic counterparts has resulted in the rapid growth of numerous
asymmetric transformations. Popularity of catalytic asymmetric reactions is due to the usage
of only less than a stoichiometric amount of the chiral control element, often the most
expensive reagent in the process. With the development of PTC, researchers placed much
effort on the development of phase transfer catalysts which could induce asymmetry into
product molecules [14]. Asymmetric PTC has been used in several types of reactions
including, Michael additions [15], Darzens reactions [16], epoxidations [17], Diels-Alder
cycloadditions [18], alkylation [19], Aldol condensations [20], and α-hydroxylation of
ketones [21]. Also, asymmetric Baylis-Hillman [22] reaction has been developed using
derivatives of quinidine to effect the reaction of activated alkenes with aldehydes.
Asymmetric phase-transfer catalysis has attracted considerable attention as a convenient
technique for the synthesis of chiral molecules. Cinchona alkaloids and ephedrine derived
catalysts are the most popular chiral PTC that has been employed to achieve the goal for
inducing asymmetry into product molecules. Chiral centers in catalysts derived from the
cinchona alkaloids are located both on the quaternary nitrogen and on the carbon framework
[23]. In addition, Merrifield resin-bound cinchonidine and cinchonine have been employed as
recoverable PTC catalysts [24, 25]. Furthermore, non-Cinchona chiral catalysts, such as
TADDOL [26], spiro ammonium [27] and phosphonium salts [28], binaphthyl derived amines
[29,30], and salen-metal complexes [31] have also been used in asymmetric PTC alkylations.
Table 1. Frequently Employed PT Agents
PTC Cost
Activity and Recovery of Catalyst Stability and Utility
Agent
Crown ethers Highly active catalysts even under Stable and frequently Very Costlier
basic conditions and at higher employed.
temperatures. Recovery is difficult
and their toxicity poses
environmental pollution.
Cryptands Highly reactive, except in the Stable. Used sometimes Costlier
presence of strong acids. despite high costs and toxicity,
due to higher reactivity.
Quternary Recovery is relatively Fairly stable under basic Inexpensive

Ammonium complicated and moderately conditions and up to 100 oC.
salts active. Extensively used.
PEG Lower in activity and can be More stable than quaternary Inexpensive
recovered easily. ammonium salts hence often
used.
Quternary Fairly active and recovery is Thermally more stable than Expensive than
Phosphonium relatively difficult. quaternary ammonium salts, quaternary
salts but less stable under basic ammonium
conditions. And widely used. salts.
Phase Transfer
Catalysis
Insoluble Soluble PTC IPTC

PTC
RPTC
LLPTC SLPTC LLPTC SLPTC GLPTC
Figure 1. Classification of PTC Reactions.

Classification of PTC
PTC reactions can be broadly classified into two main classes: soluble PTC and insoluble
PTC (Figure 1). Within each class, depending on the actual phases involved, reactions are
further classified as liquid-liquid PTC (LLPTC), gas-liquid PTC (GLPTC), and solid-liquid
PTC (SLPTC). In some cases, the PT catalyst forms a separate liquid phase, and this variant
of PTC can be grouped along with traditional insoluble PTC, where the PT catalyst is
immobilized on a solid support. Other non-typical variants of PTC include inverse PTC
(IPTC) and reverse PTC (RPTC) via a reverse transfer mechanism.
Mechanism of Phase Transfer Catalysis
Mechanism of PTC is broadly classified into two types based on kinetic criteria.
Accordingly, two main mechanisms have been recognized in phase-transfer reactions: (a) the
interfacial mechanism, typical in reactions promoted by alkali, where interfacial
deprotonation converts an anion (such as a carbanion, oxanion or azanion), which is slowly
extracted into the organic phase to swiftly react with an electrophilic substrate (Scheme 1a)
and (b) the extraction mechanism where anions are rapidly transferred as ion-pairs from
aqueous or solid phase into the organic phase where they slowly react with a substrate
(Scheme 1b).
a)
RX Q+Y- RY Q+Y-
Organic Phase
M+X- Q+Y- M+Y- Q+X- Interface
Aqueous Phase
M+X- M+Y-
b)
RX Q+Y- RY Q+Y-
Organic Phase
M+X- Q+Y- M+Y- Q+X- Aqueous Phase
Scheme 1. Two types of PTC mechanism a) Interfacial mechanism b) Extraction Mechanism.
The distinction between these two mechanisms is always made based on influence of
stirring speed and value of energy of activation [7, 9-13, 32]. To differentiate between the two
mechanisms, kinetic run at significantly higher agitation speed is required, since the
chemically controlled extraction mechanism is independent of the stirring speed above a
certain value whereas the interfacial mechanism is strongly dependent on stirring speed.
Further, to distinguish between the diffusion-controlled mechanism and other PTC/OH-
mechanisms, the kinetic order and the energy of activation of the reaction become valid. If the
energy of activation is above 10 kcal mol-1, then the mechanism operative is interfacial
mechanism and extraction mechanism is operative if it is below 10 kcal mol-1.
INGENIOUS TECHNIQUES IN CONJUNCTION WITH PHASE

TRANSFER CATALYSIS
Phase transfer catalysis will be of curiosity to anyone working in academia and industry
that needs an up-to-date critical analysis and summary of catalysis research and applications.
Currently, ingenious new analytical and process experimental techniques viz., ultrasound and
microwave irradiation assisted PTC transformations have become immensely popular in
promoting various organic reactions.
Inventing selective, efficient and eco-friendly methods for applications in complex
organic synthetic manipulations constitutes a major chemical research effort. In this regard,
several non-conventional methods are emerging that involve reactions in aqueous media [33]
or those that are accelerated by exposure to microwave [34-36] or ultrasound [37–39]
irradiation. These methods are now recognized as viable environmentally benign alternatives
[34–39]. Although, sonication methods have been initially applied to homogeneous reactions
in a variety of solvents, this approach has now evolved into a useful technique in
heterogeneous reactions. A vast majority of sonochemical applications in the synthesis deal
with reactions involving metals [38, 40] organic phase insoluble reagents, or their aqueous
solutions [38, 41-42]. Compared with the traditional methods, a large number of organic
reactions can be carried out in higher yields, shorter reaction time and milder reaction
conditions under ultrasonic irradiation [43].
Ultrasound irradiation is a transmission of a sound wave through a medium and is
regarded as a form of energy for the excitation of reactants consequently enhancing the rate of
diffusion [44-46]. Richards and Loomis [47] reported, on the chemical effects of high-power
ultrasound, two types of chemical reaction: (i) the acceleration of conventional reactions by
ultrasound and (ii) redox processes in aqueous solutions. In a liquid medium, the effects of
ultrasound are produced due to the phenomenon called cavitation. When a liquid is irradiated
by ultrasound, microbubbles can appear, grow and oscillate extremely quickly and even
collapse violently if the acoustic pressure is high enough. The occurrence of these collapses
near a solid surface will generate microjets and shock waves [48]. Moreover, in the liquid
phase surrounding the particles, high micromixing will increase the heat and mass transfer
and even the diffusion of species inside the pores of the solid [49].
Application of ultrasonic waves in organic synthesis (homogeneous and heterogeneous
reactions) has been boosted in recent years [50-55]. Sonication of multiphase systems
accelerates the reaction by ensuring a better contact between the different phases [56-57].
Further, they also increase the reaction rate and avoid the use of high reaction temperatures
[58]. These days this environmental benign technology is combined with PTC with primary
objective of optimizing reaction conditions [59-61].
Sonoication has been found to enhance this reaction of liquid–liquid phase-transfer
catalysts (LLPTC) bi-phase system. In uncatalyzed sonicated reactions, the chemical effects
of ultrasound, attributed to intense local conditions generated due to cavitation bubble
dynamics, i.e., the nucleation, formation, disappearance, and coalescence of vapour or gas
bubbles in the ultrasonic field [62, 63]. The rate enhancement in PTC assisted reactions is due
to mechanical effects, mainly through an enhancement in mass transfer. However in
ultrasound in conjunction with PTC reactions systems, cavitational collapse near the liquid–
liquid interface disrupts the interface and impels jets of one liquid into the other, forming fine
emulsions, and leading to a dramatic increase in the interfacial contact area across which
transfer of species can take place [64]. It has been reported that a combination of PTC and
ultrasound is often better than either of the two techniques alone [65, 66]. In such cases, the
phase-transfer catalyst initiates the reaction by the transfer of species across the interface and
ultrasound merely facilitates this transfer, possibly by increasing the interfacial area across
which this transfer occurs [67].
Microwaves are electromagnetic with wavelengths ranging from as long as one meter to
as short as one millimeter, or equivalently, with frequencies between 300 MHz (0.3 GHz) and
300 GHz. Microwave methodology is a novel approach towards clean and green chemistry
and it is relatively a very convenient, safe and rapid methodology. Due to these features,
microwave irradiation has been increasingly used as a synthetic tool in a number of studies.
Even after a slow uptake of the technology, which has been attributed to its initial lack of
controllability and reproducibility coupled with a general lack of understanding of the basics
of microwave dielectric heating, there has been significant number of papers have appeared
[68–74]. Researchers have shown much interest in microwave-assisted chemistry to facilitate
faster reactions and efforts are now being made to scale up reactions using this technology
[75-77].
It has become recognized that many chemical reactions, which require heating are likely
to proceed more rapidly using this different form of heating. Apart from their impact in
mainstream organic synthesis, their influence in the field of medicinal chemistry [78-82],
nanoparticle synthesis [83] etc., has been dramatic. The area is still burgeoning and this is in
no small part due to the positive interaction between suppliers of microwave equipment and
the research community. Significant advantage of microwave-enhanced chemistry is the
reduction in the reaction times. It is clear that microwave chemistry can provide access to
synthetic transformations, which may be prohibitively long or low yielding using
conventional heating.
Now a days there has been considerable interest in microwave assisted PTC reactions
[84-98]. Rates of PTC reactions, as well as selectivity of the desired product, can be
synergistically enhanced by using microwave irradiation. The resultant advantages in
comparison to classical heating are especially spectacular. The application of microwave
radiation-PTC offers new alternatives in sample preparation in terms of shorter reaction times
and reduced solvent consumption.
SCOPE AND OBJECTIVES

In principle, we wanted to present in this chapter the application of recent PTC
methodologies to the synthetically important organic reactions. Alkylation reactions,
epoxidation, esterfication, Heck reaction, cyanation, Michael reaction, darzen’s reaction,
Suzuki coupling, aziridine reaction and polymerization reactions, among others, were the
reactions originally to be covered. Because of the abundant literature found on these topics,
however, we decided to dedicate this first part only to the alkylation reactions, Heck reaction,
aziridine reaction, epoxidation, and esterfication whereas the rest of the reactions will be
studied in the second part in due course. The chapter is organized according to the sub-
headings presented in the following section, taking into account the different components and
variety of conditions involved in the each of these reactions. Further, many of the
contributions to this review are also analyzed from a critical point of view, with the aim of
discussing the advantages and disadvantages that the different techniques offer and trying to
select the best choice, when possible.
ALKYLATION REACTIONS
PTC catalyzed alkylation is an important process step in the manufacture of large number
of drugs [99]. These days chemist show much interests in imide derivatives because of their
numerous applications in biology [100,101] as well as synthetic [102] and polymer chemistry
[103]. However, there are only a few papers [104,105] discussing the synthesis of imide
derivatives under solid-liquid PTC (SL-PTC). The main advantage of using solid-liquid
process in the reaction is to avoid the slow reaction rate due to hydration in the presence of
water. It is expected that the synthesis of imide under ultrasonic–PTC condition will be more
efficient than conventional techniques.
O
Br
KOH, PTC N
O N O
0
Solvent, 40 C KBr H2O
H O
1 2
3
Scheme 2. N-alkylation of Succinimide with 1-bromo-3-phenylpropane under S-L-PTC conditions.
Recently, ultrasonic-PTC assisted synthesis of 1-(3-phenylpropyl)pyrrolidine-2,5-dione

(3) was successfully carried out by the reaction of succinimide (1) with 1-bromo-3-
phenylpropane (2) in a small amount of KOH and organic solvent under solid-liquid phase-
transfer catalysis condition [106] almost water free conditions [Scheme 2]. We investigated
systematic kinetics of the reaction and predicted the reaction mechanism. Results indicate that
the mass transfer resistance at the solid-liquid interface could be ignored when the agitation
speed exceeds 200 rpm. The overall reaction was described by pseudo-first-order kinetics and
the apparent activation energy in cyclohexanone was found to be 15.01 kcal/mol.
The influence of the amount of tetrabutylammonium bromide on the apparent rate
constant (kapp) was studied in range 0.0-0.65 g under ultrasonic standard reaction condition.
From the plot of –ln(1-x) versus time (Figure 2) it is clear that the apparent rate constant
increased linearly with the increase in the amount of TBAB catalyst. In the control
experiments (absence of TBAB), a conversion of 3.99% was observed after 2 h of reaction.
On the other hand, when a small quantity of TBAB (0.05 g) was added to the reaction
solution the conversion increased dramatically to 30.97% after 2 h of reaction. The

concentration of quaternary ammonium cation (Q+) in organic phase solution, which affected
the concentration of the active catalyst SUC-Q(org), was increased with the increased amount
of TBAB catalyst. Thus, on increasing the amount of catalysts the kapp values increases (Table
2).
5
Amount of TBAB
0g
0.05 g
4 0.15 g
0.25 g
0.45 g
3 0.65 g
-Ln(1-X)
0
0 20 40 60 80 100 120
Time (min)
Figure 2. Effect of amount of TBAB on the rate of the reaction. 6.0 × 10-2 mol of succinimide, 6.0 ×
10-3 mol of 1-bromo-3-phenylpropane, 1 g of KOH, 60 mL of cyclohexanone, 0.3 g of internal
standard (naphthalene), 45 °C, 800 rpm, 40 kHz (300 W).
Table 2. Influence of the amount of TBAB catalyst on the apparent rate constants,
(kapp) a
Amount of TBAB (g) Apparent Rate Constant kapp (x 10-3 min-1)

0 0.4
0.05 3.1
0.15 7.1
0.25 12.4
0.45 23
0.65 32
a Reaction conditions: 6.0× 10-2 mol of succinimide, 6.0 × 10-3 mol of 1-bromo-3-phenylpropane, 1 g of
KOH, 60 mL of cyclohexanone, 0.3 g of internal standard (naphthalene), 45 °C, 800 rpm, 40 kHz,
(300 W).
In order to investigate the influence of ultrasonic frequency on the PTC catalyzed

alkyalation of succinmide, the reaction rates at 40 kHz and 120 kHz were compared with
same output power of 300 W. The results are shown in Figure 3 and Table 3. In silent
condition, the conversion is only 62% (kapp = 8 × 10-3 min-1), but in the presence of ultrasound
the conversion is 76% (kapp = 12.4 ×10-3 min-1) and 90% (kapp = 19.3 ×10-3 min-1) for 40 and
120 kHz, respectively. Thus, the ultrasonic effect enhances the rate 1.55 times with respect to
the conventional method (agitation speed at 800 rpm only). From these observed results it is
clear that the ultrasonic assisted phase-transfer catalysis significantly increased the reaction
rate.
2.5
Ultrasound frequency
0 kHz
40 kHz
2.0 120 kHz
1.5
-Ln(1-X )
1.0
0.5
0.0
0 20 40 60 80 100 120
Time (min)
Figure 3. Plot of -ln(1 - X) of 1-bromo-3-phenylpropane versus time with various ultrasound frequency;
6.0 × 10-2 mol of succinimide, 6.0 × 10-3 mol of bromo-3-phenylpropane, 1 g of KOH, 60 mL of
cyclohexanone, 0.3 g of internal standard (naphthalene), 0.25 g of TBAB, 45 °C, 800 rpm.
Table 3. Influence of different ultrasound frequencies on the apparent rate constants

(kapp) a
Ultrsound Frequency (kHz) Apparent Rate Constant kapp (x 10-3 min-1)

0 8
40 12.4
120 19.3
a Reaction conditions: 6.0 × 10-2 mol of succinimide, 6.0 × 10-3 mol of 1-bromo-3-phenylpropane, 1 g
of KOH, 60 mL of cyclohexanone, 0.3 g of internal standard (naphthalene), 0.25 g of TBAB, 45
°C, 800 rpm (300 W).
Further we found that, the reaction rate is increased by increasing the amount of KOH
and amount of SUC-H. However, the reaction rate is decreased by increasing the volume of
water and cyclohexanone. We compared the influence of six solvents on the reaction and the
order of reactivities of the six solvents is: cyclohexanone > acetophenone > o-
dichlorobenzene > chlorobenzene > chloroform > toluene. Among the various PTC’s tested
tetraoctylammonium bromide (TOAB) showed significantly higher catalytic activity.
Chiral nanosize molecules, derived from cinchonidine and Fréchet dendritic wedges up to
generation three, have been synthesized by Guillena et. al., [107] and demonstrated that these
dendritic cinchonidine ammonium salts (Scheme 3) can be applied as phase transfer catalysts
in the alkylation of N(diphenyliminemethylene)glycine (Scheme 4). For first generation
catalysts a reversal on the stereoselectivity can be achieved by changing the nature of the
inorganic base from KOH to NaOH. The study reveals efficiency of the catalysts are by
reaching a moderate level of asymmetric induction, while the chiroptical properties are
independent of the enantioselection achieved. By employing dialysis membranes satisfactory
results have been obtained in the recovery and reuse of higher generation salts.
Br- OR1
N
+
OR2
N OR1
4
a; R1 = Bn, R2 = H
b; R1 = Bn, R2 = Allyl
c; R1 = Bn, R2 = Bn
d; R1 = Me, R2 = H
Scheme 3. Chiral dendritic molecules used as phase transfer catalysts in the alkylation of a glycine
imine ester.
Ph Ph
Cat (10 mol%), PhCH2Br, Base N
N * CO2iPr
Ph CO2iPr Solvent, T( C)o Ph
5 6
Ph
Scheme 4. Alkylation of N(diphenyliminemethylene)glycine (5) with benzylbromide catalyzed by a

new dendritic cinchonidine-derived ammonium salt (4a).
The development of more efficient PTC’s is an important goal in organic synthesis so as

to increase the catalytic efficiency of these catalysts. In this regard, one of the options is to
increase the number of catalytic active sites in them. This led to the invention of multi-site
phase transfer catalysts. Recently, Vivekanand and Balakrishnan [10] have synthesized and
characterized a novel multi-site phase transfer reagent, viz., 1,3,5-tris((N,N,N-
triethylammonioum) methylphenyl)benzene trichloride (TEAMPBTC) and studied its utility
in the synthesis of 2-(2-bromoethyl)-5,5- dimethylcyclohexane-1,3-dione by selective

monoalkylation of dimedone under pseudo-first order reaction conditions. Further, they
investigated the catalytic activity of a new quaternary ammonium salt, with three active sites,
in the cycloalkylation of indene with 1,4-dibromobutane under pseudo-first order condition
[11]. They found the catalytic activity of the new onium salt is superior compared to other
commercial phase transfer catalysts under mild reaction conditions.
The substitution of alkyl bromides (RBr) to sodium sulfide (Na2S), including linear and
branched alkyl groups catalyzed by phase-transfer catalysts in combination with ultrasound
obviously provides a more efficient synthetic approach for the preparation of thioethers [60].
We investigated a comprehensive kinetic study of thioether synthesis under influence of
ultrasound assisted phase-transfer catalysis conditions. Mechanism of PTC assisted thioether
synthesis is presented in Scheme 5. These PTC reactions were carried out in a liquid–liquid
two-phase medium. High yields of products were obtained in shorter reaction time using 4
mol% of the tetrabutylammonium bromide and ultrasound 28 kHz (200 W) conditions.
However, in the absence of a phase-transfer catalyst and ultrasound, less than 5% conversion
was detected even after 4 h of reaction.
2RBr R2S
Organic Phase
2RBr + (Q+)2S 2Q+Br-+ R2S (2)
Interface
+ - +
2Na Br + (Q )2S 2Q+Br- + Na2S
(1)
Aqueous Phase
2Na+Br- Na2S
Scheme 5. PTC mechanism for the thioether synthesis.
Rate of the two-phase reaction is influenced by the mass transfer as well as the chemical
reaction. The effect of the agitation speed on the reaction rate is shown in Table 4. For
agitation speed over 400 rpm, the rate of the reaction is insensitive to the agitation speed. This
can be attributed to the active intermediate of the catalyst (Q2S), which is hydrophobic and
likes to stay in the organic phase, i.e., it is easy to transfer the active intermediate of the
catalyst from the aqueous phase to the organic phase, in which the interfacial area is not so
important. Thus, the mass transfer rate reaches a constant value when the stirring speed is
larger than 400 rpm. In the absence of stirring speed and in the presence of the effect of
ultrasonic condition at 28 kHz (200 W) the observed rate constant is 9.8×10−3 min−1 and in
vice-versa the kapp value at 500 rpm is 11.4×10−3 min−1. In the presence of both condition, i.e.,
at 500 rpm combined with the ultrasonic wave frequency 28 kHz (200 W) the kapp value is
41.7×10−3 min−1. From this observation, we infer that the ultrasonic effect enhances the rate
3.7 times with respect to the conventional method (stirring speed at 500 rpm only). Further,
presence of ultrasonicwave results in increase in the collision rate between the organic and
aqueous phase reactants and decrease the surface area between the two layers [108].
Table 4. Influence of the agitation speed on the apparent rate constants, kapp: 7g Na2S;
10 mL water; 4 mmol of 1-butyl bromide; 40 mL n-hexane, 4 mol% of TBAB; 500 rpm;
35 0C; 60 min of reaction.
Agitation Speed (rpm) kapp (x 10-3 min-1)

0 9.8
200 33.9
400 39.6
500 41.7
600 40.7
800 40.8
1000 40.6
Figure 4. Conversions of various reactants with time: 7 g Na2S; 10 mL water; 40 mL of n-hexane; 4

mol% of TBAB; 0.5 g of biphenyl; 500 rpm; 35 0C; 60 min of reaction.
Influence of different alkylating agents on the rate of thioether synthesis is presented in

Fig. 4 and Table 5. The reaction follows pseudo-first order law in the presence of PTC and
excess amount of sodium sulfide. The kinetic investigation reveals that the most reactive
organic reactant is allyl bromide and the reaction is 100% completed within 10 min for allyl
bromide. It can be attribute to the the smaller molecular size and the conjugation of pi-bond.
From 1-propyl bromide (1-C3H7Br) to 1-octyl bromide (1-C8H17Br) the kapp value decreases
due to increasing the carbon chain of the molecules and (Q2S) is not able to properly interact
with active site of the long chain alkyl bromides. Among the alkyl bromides sec-propyl
bromide (2-C3H7Br) is the least reactive one because of steric hindrance in its reaction.
Table 5. Influence of alkylating agents on kapp: 7 g Na2S; 10 mL water; 4 mmol of 1-

butyl bromide; 40 mL of n-hexane; 4 mol% of TBAB; 500 rpm; 35 0C; 60 min of
reactiona (200 W).
Alkyl Bromide kapp (x 10-3 min-1)

1-Propyl bromide 49.6
1-Butyl Bromide 41.7
1-Pentyl bromide 25.5
1-Hexyl bromide 17.1
1-Heptyl bromide 11.7
1-Octyl bromide 9.5
2-Propyl bromide 5.6
Allyl bromidea -
a- Reaction completed within 10 min.
Figure 5. Influence of ultrasonic frequenzy on the conversion of 1-butyl bromide: 7 g Na2S; 10 mL

water; 4 mmol of 1-butyl bromide; 40 ml of n-hexane; 4 mol% of TBAB;0.5 g of biphenyl; 500 rpm; 35
0C; 60 min of reaction.
Further, we compared the reaction rate at 28 kHz and 40 kHz having same output power
of 200W. At 1 h, without ultrasonic irradiation the conversion is only 53%, but in the
presence of ultrasonic the conversion is 91% and 97% for 28 kHz and 40 kHz, respectively
(Fig. 5). These observed results indicate that ultrasonicassisted phase-transfer catalysis
significantly increased the yield of the products. The same trend is also observed by Entezari
and coworkers [109,110]. So the application of ultrasounds in organic synthesis is one of the
popular areas in sonochemistry.
Selective mono alkylation of isosorbide and isomannide was carried using
tetrabutylammonium bromide and by using potassium hydroxide as a base by Chatti et al.
[111a]. Further, O-alkylation of mono-benzylated isosorbide and isomannide was performed
with various α,ω-dihalides or ditosylates using tetrabutylammonium bromide as phase
transfer agent under microwave condition [111b]. In addition to the expected ethers 8 (a and
b), some amounts of alkene 9 (a and b) were obtained resulting from a dehydrobromination
on the common intermediate involved in SN2±E2 competitive processes. The ambient
reaction conditions (70% yield) involve the use of only 2% of catalyst in p-xylene for 5 min
at 140 0C or in toluene for 15 min at 110 0C. In order to minimize the competitive
elimination, halide leaving group was changed to tosylate when competitive SN2±E2
processes is involved (Scheme 6).
HO Br-(CH2)8 O
O O
KOH, TBAB
+ Br-(CH2)8-Br
O O
OCH2Ph OCH2Ph
7a
7b
CH2=CH-(CH2)6 O
O O (CH2)8 O
O O
O +
OCH2Ph O O
PhCH2O OCH2Ph
9a 8a
9b 8b
Scheme 6. Alkylation of isosorbide and isomannide performed under microwave assisted phase transfer
catalysis condition.
2-Benzyloxyacetophenone (12) is utilized as a pharmaceutical intermediate for the

manufacture of drugs such as antiaggregant, antihypertensive, platelet, lipoxygenase,
diuretics, prostaglandin and, analgesics and for treatment of metabolic disorders. Novelties of
low power microwave irradiated solid–liquid phase transfer catalysis have been brought out
in the selective O-alkylation of sodium salt of o-hydroxyacetophenone (OHAP, 10) with
benzyl chloride (11) (Scheme 7) by using tetra-n-butylammonium bromide as a catalyst by
Yadav et al. [112]. Authors indicate that microwave-PTC condition enhances the rate of the
reaction. The conversion increased only upto a certain concentration of TBAB (6.7 × 10−5 mol
cm-3). Above this concentration there was no further increase in the conversion. Authors
attribute this to the fact that the reaction rate was fast and thus, mass transfer of ion pair from
the liquid film to the bulk liquid was controlling beyond certain concentration of catalyst.
Here the rate of mass transfer was less than the rate of reaction. On comparing four PTC’s
viz., tetra-n-butylammonium bromide (TBAB), tetra-n-butylammonium hydrogensulfate
(TBAHS), tetra-n-propylammonium bromide (TPAB) and tetra-n-butylammonium iodide
(TBAI), TBAB was found to more efficient catalyst for the reaction under study. This is a
solid–liquid PTC process in which the entire catalyst is in the organic liquid phase. The type
of cations and anions present in the system greatly influences the solubility of solid
nucleophile. In fact, the PTC breaks the crystal lattice and transports the nucleophile as Q+Y−
whose concentration depends on the type of PTC used. This is the case of homogeneous
solubilization. Therefore, the activity of TBAB is much greater. The system elegantly forms a
synergistic combination of S–L PTC and microwave irradiation. The Gibbs free energy for
solid dissolution with anion exchange reaction could be also evaluated.
Cl O
O ONa
PTC/Solvent O
+ + NaCl
MW
10 11 12
Scheme 7 O-alkylation of o-Hydroxyacetophenone under MW-PTC condition.
Lee et al. [113] showed that the treatment of phenols (14) with nitroaryl fluorides (15),
KF-alumina and Aliquat 336 under microwave irradiation in a domestic microwave oven
afforded corresponding diaryl ethers (15) in high yields. Control experiments (absence of
PTC’s) resulted in small yield of ethers. Comprehensive screening of several phase transfer
catalysts (Aliquat 336, 18-crown-6, and TBAB) together with various inorganic bases
(K2CO3, CsF-Celite, and KF-alumina) in microwave promoted arylation reactions, reagents
combination of 40% w/w potassium fluoride on alumina with Aliquat 336 appeared to be the
most optimum reaction system in terms of yield and convenience. They reported sluggish
reaction for the same arylation reactions with KF-alumina/ 18-crown-6 in acetonitrile reaction
system even when the reaction is allowed for 84 h.
OH O-Ar
KF-alumina/Alumina
ArF
MW, 10 min
R 13 14 15
Scheme 8. O-alkylation of substituted phenols under MW-PTC condition.
Ethers are commercially attractive because of their extensive applications in the fine
chemicals industry, such as anti-inflammatory, analgesic, and antipyretic drugs
[114], ecologically clean additives to motor oils, non-toxic and high-octane gasoline
additives [115–117], perfumery [118] and plasticizer [119]. p-nitrophenetole was synthesized
by the reaction of p-chloronitrobenzene with potassium ethoxide in a homogeneous system
using benzyltriethylammonium chloride (BTEAC, Q+Cl-) as a phase transfer catalyst at 50 0C
under microwave irradiation conditions [120].The mechanistic details of the reaction is
presented in Scheme 9.
EtOH + KOH in situ EtO-K+ H2O

+
in situ
EtO-K+ + Q+X- EtO-Q+ + KX
(PTC) Quaternary
ammonium ethoxide
Cl O
Aromatic nucleophilic
EtO-K+ + substitution reaction + KCl
No2 No2
16 17
Cl O
Aromatic nucleophilic
substitution reaction +
EtO-Q+ + Q+X-
No2 No2
16 17
Scheme 9. Mechanism for aromatic nucleophilic substitution reaction between p-chloronitrobenzene

and ethoxide ion in the presence of PTC conditions.
In this nucleophilic substitution reaction, the comparative reactivity’s of eight different

phase-transfer catalysts, such as BTEAC, BTEAB, TBAHS, TBAC, TEAB, TBAI, TEAC
and TBAB was explored. The order of the activities for these eight quaternary ammonium
salts is TBAI< TBAB <BTEAB < TEAB < TBAC < BTEAC < TBAHS <TEAC. The
corresponding kapp values in using these quaternary ammonium salts are depicted in Table 6.
Further we have compared the reactivity of microwave-PTC assisted reaction with ultrasonic-
PTC assisted reaction and silent-PTC reaction (Table 6). Kinetic results indicate that the
microwave irradiation enhances the reaction. In general, the order of the distribution of halide
ions in the organic phase is I- > Br- > Cl-, which reflects the Starks’ extraction mechanism. In
contrast, in the ethoxylation of p-chloronitrobenzene, the order of the reactivities of the
tetrabutylammonium cation group was found to be TBAHS > TBAC > TBAB > TBAI. Thus,
smaller size of the anionic ion in the halide groups of PTC’s is favorable for a high reaction
rate. This phenomenon is more consistent with the interfacial reaction mechanism rather than
the extraction reaction mechanism. For an interfacial reaction mechanism, the reaction rate is
highly dependent on the concentration of the catalyst at the interface. For the quaternary
ammonium cations with the same halide ion (chloride and bromide), the order of the activities
of these PTC’s is TEA cation > BTEA cation > TBA cation. Hence, it is obvious that a higher
reactivity is obtained for a quaternary ammonium salt of less total carbon number. The
activity of the catalyst is dependent on the structural characteristics of a quaternary
ammonium cation. The yield of the product is correlated with the accessibility of the
quaternary ammonium salt (Q+X-), which is a function of carbon in each chain. It is thus
concluded that the order of the activities is consistent with the results indicated by Starks et
al. [121].
Table 6. Influence of phase-transfer catalysts on the apparent rate constants, kapp: 8 g,

KOH; 1 mL, water; 0.5 g, p-chloronitrobenzene; 30 mL, ethanol; 50 0C; 0.25 g, nonane;
15 min of reaction; microwave condition ; ultrasonic conditiona; silent condition.
PTC’s
TEAB TEAC TBAI TBAB TBAC TBAHS BTEAB BTEAC
kapp (x 10-2 min- 15.86 19.67 13.95 14.61 16.71 18.73 14.79 17.06
1
,M.W Cond.)
kapp (x 10-2 min- - - 2.84 2.61 2.42 1.91 1.39 0.88
1
,Ultrasonic
Cond.)
kapp (x 10-2 min- - - 2.29 1.96 1.96 1.23 0.90 0.56
1
,Silent Cond.)
a Ultrasonic condition: 28 kHz, 200 W, agitation speed 600 rpm.
20
18
16
kapp x 10 (min )
-1
2
14
12
10
0.00 0.05 0.10 0.15 0.20
Amount of BTEAC (g)
Figure 6. Influence of the amount of BTEAC on the apparent rate constants, kapp: 8 g, KOH; 1 mL,
water; 0.5 g, p-chloronitrobenzene; 30 mL, ethanol; 50 0C; 0.25 g, nonane; 15 min of reaction;
microwave condition.
In the absence of BTEAC, the conversion of p-chloronitrobenzene is low. Nonetheless,

the reaction is greatly enhanced by adding a small quantity of the BTEAC catalyst. An
optimum value of the BTEAC catalyst corresponds to a 0.1 g of BTEAC. A further increase
in the amount of BTEAC makes the conversion of p-chloronitrobenzene decrease (Fig. 6).
The decrease is probably due to the fact that the conversion of potassium ethoxide to
quaternary ammonium ethoxide reaches a new equilibrium state. At higher concentration of
Q+Cl-, the equilibrium tends to shift to the formation of potassium ethoxide and thus the
quaternary ammonium ethoxide is decreased by Le Chatelier’s principle. Hence, the
conversion of p-chloronitrobenzene is decreased with an increase in the amount of Q+Cl- at a
higher concentration.
HECK REACTION
The formation of carbon–carbon bonds is a fundamental reaction in metal-catalyzed
organic synthesis, the efficiency of which has interested organic chemists for a long time ago.
Heck reaction is one of the most popular methodologies for carbon-carbon coupling in
synthetic organic chemistry due to its high chemoselectivity and mild reaction conditions
[122]. This type of reaction is driven by the ability of Pd(0) complexes to undergo oxidative
addition to C-X (X= Cl, Br and I) bonds followed by addition to olefinic compounds
[123,124] (Scheme 10). Their mechanism are classified into two types viz., i) cationic
mechanism or and ii) a neutral mechanism [125,126]. Former type of mechanism is operative
when the X is OTf, OAc, or when Ag+, TI+, quaternary ammonium and phosphonium salts
are used to help displacement from halides. On the other hand, the neutral mechanism is
operative when X is σ-donor such as Cl, Br, or I- [127]. Owing to its mild reaction conditions,
Heck reaction is widely used in pharmaceuticals, preparation of hydrocarbons, UV screens,
polymerization chemistry, and in advanced enantioselective synthesis of natural products
[128].
Generally, the Heck reaction works best for preparation of di-substituted olefins from
mono-substituted ones and electron poor olefins tend to give higher yields. Olefins with
variety of functional groups viz., esters, ethers, carboxylic acids, nitriles, phenols, dienes, can
be employed however allylic alcohols tend to rearrange [129]. Now a days, the extensive
study of Heck-type reactions [130-132] and their application in organic synthesis has led to
the introduction of various improvements [133-135]. Addition of catalytic amount of
quaternary salt (Q+X-) accelerates the reaction rate to a great extent and selectivity of the
reaction [133,135-147].
H R1 R1 R4
Pd(0), Ligand, Base
R 4X
R2 R3 Solvent, Heat R2 3 R3
18 19 20
Scheme 10. General Heck Reaction.
In recent past, Heck reaction assisted by phase transfer catalyst (PTC) has been
developed into an efficient methodology for coupling of aryl halides with alkenes leading to
substituted alkenes. The Heck reaction is an important methodology for the introduction of
functionalized aryl moieties onto heterocyclic compounds in organic synthesis. Penalva et al.
[148] explored direct arylation of activated thiophenes (21) using a Heck type reaction with a
mixture of Pd(OAc)2 and tetra-n-butylammonium bromide as catalytic system. Unexpectedly,
the reaction resulted in competitive formation of biaryls (24) resulting from an Ullmann type
coupling (Scheme 11).
I
"Pd" NC
NC S
Base, PTC
S
21 22 23 24
Scheme 11. Heck reaction between 2-cyanothiophene and iodobenzene.
R1 EWG R1 EWG
ArX
1-4 mol % Pd(OAc)2
25 26 Ar 27
TBAC, Cy2NMe
EWG DMAC, 85-100 0C EWG
ArX
R2 Ar R2
28 26 29
R1 = H, CH2COOCH3
R2= CH3, Ar
X = Br, I
Scheme 12. Modified Heck reaction using bulky amine bases in presence of tetrabutylammonium
chloride.
The investigation reveals the influence of various parameters such as the nature of the
base and the nature and/or the amount of the phase transfer agent on the reaction selectivity.
Bases such as N, N-diisopropylethylamine leads specifically to the biaryl formation. In
presence of stoichiometric amount of tetrabutyl ammonium bromide or a stoichiometric
amount of tetraoctylammonium bromide with potassium carbonate as base, the competitive
formation of biphenyl is inhibited. On the other hand, the behavior of the
tetraalkylammonium salt is more dependent on counter ion nature than upon the alkyl chain
length and only phase transfer agent bearing a bromide as the counter ion provides an active
catalyst system than with other halide counter ions.
Gürtler and Buchwald [149] successfully explored coupling of activated olefins (25 &
28) with both electron-rich and electron-poor aryl halide (26) substrates by employing the
Pd(OAc)2/ Cy2NMe/tetraethylammonium chloride system(Scheme 12). Labeling studies
indicate that the source of this selectivity is thermodynamic in nature. Even ortho-substituted
aryl halides, whose transformations are problematic under typical reaction conditions, were
efficiently converted into the desired trisubstituted olefins under PTC condition. Nevertheless,
in these cases a greater quantity of catalyst was required. When stoichiometric quantity of
tetraethylammonium chloride is employed, the reaction proceeded with the shortest reaction
times. The method displays good stereoselectivity and a high degree of functional group
compatibility.
Palladium-catalyzed Heck coupling reaction in water in the absence of any organic
solvents using PTC-microwave technology was investigated by Wang et al. [150]. The
arylation reaction of alkenes (30) with aryl iodides (31) proceeded smoothly under microwave
irradiation to give exclusively the desired trans-products in good yield (Scheme 13).
Y R
Pd(PPh3)2Cl2,TBAB,K2CO3
+ RI
H2O, MWI Ar
30 31 Ar 32a-g
a = Ph(R), Ph(Y); b = Ph(R), COOH(Y); c = p-HO2CC6H4(R), COOMe(Y);
d = p-O2NC6H4(R), Ph(Y); e = o-O2NC6H4(R), Ph(Y); f = p-CH3C6H4(R), Ph(Y);
g = o- CH3C6H4(R), COOH(Y).
Scheme 13. Palladium and PTC catalyzed Heck cross coupling reaction under microwave irradiation.
They compared catalytic efficiency of PTC and various bases in the synthesis of stillbene
using various onium salts, including tetrabutylammounium chloride (TBAC),
tetrabutylammounium bromide (TBAB), tetrabutylammounium iodide (TBAI) and
polyethyleneglycol (PEG). The following order illustrates the relative activity of different
catalysts and bases: TBAB>TBAI>TBAC>PEG-400 & K2CO3>Na2CO3>NaHCO3>NaOH
(Table 7).
For comparison, the yields of the microwave irradiation assisted reaction and
conventional heating reaction results are summarized in Table 8. The results showed that the
synthesis of compounds 32a–g under microwave irradiation were 18–42 times faster than
conventional heating. This ratio between the reaction time using conventional reflux and
microwave irradiation (tc/tmw) under same conditions quantifies the microwave heating effect.
PTC approach proceeds most efficiently when carried out in the presence of aqueous
solution of sodium carbonate or hydroxide and catalytic amount of PT catalyst. Jeffery and
Ferberone [151] reported one pot synthesis of unsymmetrical (or symmetrical) trans-stilbene
derivatives based on two sequential PTC-Heck-type reactions effected in the presence of
tetrabutylammonium salt-based catalyst systems, using haloarenes (31) and
vinyltrimethylsilane (33) as double bond equivalent (Scheme 14). The procedure followed
results in highly chemo-, regio-, and stereoselective products.
Table 7. Influence of Catalyst (PTC) and Base on the Formation of 32aa
Base PTC Yield of 32ab

K2CO3 No PTC 30
K2CO3 PEG-400 80
K2CO3 TBAC 84
K2CO3 TBAI 90
K2CO3 TBAB 91
Na2CO3 TBAB 88
NaHCO3 TBAB 61
NaOH TBAB 52
a-The reaction was carried out in H2O at a power level of 375W for 10 min under argon; b- Isolated
yield.
Table 8. Role of Microwave and Conventional Heating in the Heck product formation
Product Microwave heating (375 W) Conventional Heating

tmw(min) Yield (%) tc(min) Yield (%) tc/tmw
32a 10 91 420 85 42
32b 10 88 180 88 18
32c 10 92 420 90 42
32d 10 89 180 80 18
32e 10 86 180 80 18
32f 10 89 420 84 42
32g 10 93 300 54 30
1)cat.Pd(dba)2, KF, Ar'

TBAC, Toluene, Room Temp.
SiMe3 ArI
2) removal of excess CH2-CHSiMe3
33 31 3)cat.PR3 or without PR3 Ar
34
Ar'X, DMF, K2CO3
65-105 0C
Scheme 14. PTC assisted palladium-catalyzed synthesis of unsymmetrical stilbene derivatives.

Unsymmetrical trans-stilbenes (34) obtained in high yields by treating aryl iodide with an
excess of vinyltrimethylsilane, in the presence of potassium fluoride, tetra-n-butylammonium
chloride and catalytic amounts of bis(dibenzylideneacetone)palladium (Scheme 14). In order
to effect second Heck reaction the excess of vinyltrimethylsilane (33) was then removed
under reduced pressure. The second Heck reaction was realized in wet N,N-
dimethylformamide, in the presence of already present palladium catalyst and tetra-n-
butylammonium chloride system and added potassium carbonate. This second step can be
carried out either in presence or absence of phosphine ligand at room temperature (Table 9,
entries 1–3). Further, heteroaromatic trans-stilbenes can be synthesized using this
methodology (Table 9, entries 4–6). GC–MS analyses of the reaction mixtures indicated a
nearly exclusive formation of stilbene derivatives, with a very high isomeric selectivity for
the (E) configuration ranging between 96 and 99%.
Table 9. Comparative yields of unsymmetrical stilbene derivatives synthesized

by Heck reaction.
Entry Ar-X (31) Ar’-X (31’) PR3/Pdb Temp (o C) Product Yield

(34) [%][b]
Ar'
I I
1 0 65 Ar 90
Ar= 4-OMeC6H4
MeO Cl Ar'= 4-ClC6H4
I Ar'
I
0 85 60
2 Ar
Cl 2 65 Ar= 4-ClC6H4 (96)

Ar'= 2-naphthyl
Ar'
I I
72
3 0 65 Ar
Cl MeO Ar= 4-ClC6H4 (94)

Ar'= 4-OMeC6H4
I Ar'
66
4 I 2 85 Ar
S Ar= 2-thienyl (80)
Ar'= 2-naphthyl
Br Ar'
60
5 I 2.5 105 Ar
S N Ar= 2-thienyl (84)
Ar'= 4-N(Me)2-C6H4
Ar'
I
72
6 I 0 65 Ar
S MeO Ar= 2-thienyl (94)
Ar'= 4-OMe-C6H4
Similarly symmetrical stilbene derivatives were synthesized by treating of 2 equiv. of an

aryl iodide (31) with 1 equiv. of vinyltrimethylsilane (33) and were followed by arylation in
wet DMF in the presence of palladium catalyst and tetra-n-butylammonium chloride (already
present in the reaction mixture) and potassium carbonate (added), with or without
triarylphosphine. Stilbene derivatives with a very high isomeric selectivity ranging between
95 and 99% were formed. The authors further confirmed the potential and efficiency of the
described methodology by a concise, convenient, highly chemo-, regio-, and stereoselective
synthesis of resveratrol (trans-3,5,4-trihydroxystilbene).
AZIRIDINES
Aziridines are organic compounds containing one amine group and two methylene
groups and are constituents of several molecules presenting biological activity, for example,
azinomycins and mytomycins [152]. These nitrogen-containing heterocyclic compounds are
frequently show up as substructures in natural products and also show potent biological
activities[153]. For that reason, chemists would like to develop practical and convenient
methods for constructing aziridine compounds. Researchers are particularly interested in
terminal aziridines due to their facile ring-opening with various nucleophiles [154]. Synthesis
of aziridines by conventional methods suffers from several disadvantages such as long
reaction time, use of toxic and organic solvent, difficulty of recovery of high boiling solvent
relative to the stability of aziridines, high reaction temperature and use of additives [155]. In
this regard PTC methodology is can be applied in the synthesis of aziridines.
Rolf Carlson et al. [156] have developed a practical, highly efficient and simple
aziridinaton protocol for α-bromo-2-cyclopenetenone derivatives 35 (Scheme 15). Also they
have assessed different reaction conditions to apply tandem conjugate addition initiated ring
closure (CAIRC) reactions and reported the synthesis of N-substituted bicyclic-a-keto-
aziridines (37) from a series of primary amines (36) applying eight different PTC’s
particularly using tetrabutylammonium bromide, TBAB in H2O (Table 10). Most of the
reactions gave similar results using various PTCs.
O O
TBAB, H2O H
Br RNH2
rt N
H R
35 36(a-h) 37(a-h)
R = phenylethyl(a), benzyl(b), furayl(c), cyclohexyl(d), allyl(e), propyl(f),

butyl(g) and tert-butyl amine(h)
Scheme 15. Aziridinaton α-bromo-2-cyclopenetenone using PTC protocol
Table 10. Effect of different some phase transfer catalysts on aziridination of -bromo-2-
cyclopenetenone in the presence of H2O at room temperature.
Entry No. PTC Yield of 37b (%)

1 Benzyldimethyl 2-hydroxymethylammonium chloride 89
2 Tetrabutylammonium fluoride 54
3 Tetrabutylammonium iodide 88
4 Tetrabutylammonium terafluroborate 79
5 Tetrabutylammonium hydrogen sulphate 82
6 Tetrahexylammonium bromide 87
7 Benzyltriethylammonium chloride 74
8 Tetrabutylammonium bromide 91
Especially, the aziridination reactions mediated by benzyldimethyl-2-hydroxyethyl

ammonium chloride, Bu4NI, Hex4NBr and Bu4NBr (entries 1, 3, 6 and 8, respectively)
proceeded in a similar manner with good to excellent yields.
Table 11. Influence of various aliphatic primary amines on aziridination of -bromo-2-

cyclopenetenone in presence of TBAB.
Entry No. Amine Time (h) Product Yield(%)

1 35b 5 O 93
N
37b
2 35a 5 O 98
N
37a
3 35c 5 O 91
o
N
37c
4 35d 3 O 90
N
37d
5 35e 3 O 96
N
37e
6 35 h 3 O 97
N
37h
7 35f 3 O 95
N
37f
8 35g 1 O 94
N
37g
Further they examined the role of various aliphatic primary amines 35a–h (phenylethyl,
benzyl, furayl, cyclohexyl, allyl, propyl, butyl and tert-butyl amines, respectively) in the
aziridination of α-bromo-2-cyclopenetenone under PTC condition and observed excellent
reactivity with all the tested amines (Table 11). Particularly, the reaction of t-BuNH2 (35h)
was very fast and the reaction was completed within 1 h.
Cyclization of 3-Arylamino-2-chloropropane nitriles, obtained by the interaction of
arylamines with α-chloroacrylontrile, is an efficient method under PTC condition to prepare
N-aryl-2-cyanoaziridines [157].
In general, phase transfer catalysis in presence of nitrogen- and phosphorus-based

catalysts is carried out under strongly basic and nucleophilic conditions. Hence their utility
under these strenuous conditions is well understood. Researchers have seldom employed
carbocations as phase transfer agent under such conditions. Previous reports indicate the
possibility of synthesis of stable carbocations [158]. Stable carbocations and
triazatriangulenium ions were synthesized starting from tris(2,6-dimethoxyphenyl)carbenium
ion and primary alkylamines [159-164]. Recently, there is an upsurge in interest in catalytic
community about utility of these triazatriangulenium ions as phase transfer agent. Nicolas and
Lacour [165] explored its utility in several classical PTC reactions and compared their
efficiency to that of tetrabutylammonium bromide and 18-crown-6. In order to understand the
partition ability, hydrophilicity and lipophilicity, they synthesized several triazatriangulenium
cations bearing alkyl side chains of various lengths and polar/apolar character (Scheme 16)
and followed various organic reactions viz., aziridination, dichlorocarbene addition, ester
alkylation and alkene epoxidation.
MeO OMe R R
OMe OMe R-NH2 (excess) N N
+ 170-180 oC +
O O N
MeMe 39 [BF4] R
38 [BF4] 39a; R = (CH2)OH 41%
39b; R = (CH2)CH3 40%
39c; R = (CH2)5CH3 44%
39d; R = (CH2)7CH3 44%
Scheme 16. Synthesis of Triazatriangulenium Salts, [39a] [BF4]-[39d] [BF4].
Catalytic efficiency (Scheme 17 & Table 12) of these triazatriangulenium Cations were
compared with TBAB in aziridine reaction of styrene (40) with a mixture of Chloramine-T
(41) and diiodine by following Minakata and Komatsu protocol [166]. The order of the
activities for these catalysts after five hours of reaction : [39a][BF4] < [39b][ BF4] < [39d][
BF4] < [39c][ BF4] < TBAB. Higher conversions and yields (80 and 85%) were reported by
the authors by extending the reaction time to 15 and 24 h with salts TBAB and [39c][BF4],
respectively.
O Cl Ts
C6H5 cat.(10 mol%), I2 N
+ S N
Na
O CH2Cl2 :H2O
C6H5
40 41 20 0 C
42
Scheme 17. Aziridinaton of styrene (40) with chloramine-T (41) using PTC protocol.
Table 12. Aziridination of Styrene by Chloramine-T/I2 under PTC condition.
Entry Catalyst Time(h) Yield (%) Conversion (%)

1 TBAB 5 30 37
2 [39a][BF4] 5 5 7
3 [39b][BF4] 5 7 9
4 [39c][BF4] 5 23 28
5 [39d][BF4] 5 16 20
6 TBAB 15 80 95
7 [39c][BF4] 24 85 100
8 no 5 3 5
PhCH2N+Et3 Cl- (10 mol%) Cbz

Cl Cbz N
+ N O
MeCN, RT, 2 h
O Na
43a (2 equiv) 44 44: 80%
NaCl
PhCH2N+Et3 Cl-
Cl
Cl Cbz
N
_ N Cbz
O
_O
PhCH2N+Et3 PhCH2N+Et3
Scheme 18. Mechanism of aziridination of methyl vinyl ketone (43a) and chloramine- Cbz (44 ).
Minakata et al. [167] developed a simple synthetic method for the catalytic aziridination
of electron deficient olefins with N-chloro-N-sodio benzyl carbamate based on solid–liquid
phase-transfer catalysis using BTEAC as phase transfer agent. Aziridination reaction between
methyl vinyl ketone (43a) and chloramine- Cbz (44), was followed by using 10 mol % of
BTEAC under solid–liquid phase-transfer catalysis condition, afforded the aziridine product
in 80% yield in 2 hours and for this reaction they proposed a rational mechanism. Initially, the
sodium ion of chloramine- Cbz (44) is exchanged for an ammonium ion, subsequent Michael
addition of the soluble nitrogen species to the enone gives the enolate and finally
intramolecular cyclization affords the desired aziridine (Scheme 18).
The successfully extended this protocol to Methyl acrylate (43b) and phenyl vinyl
sulfone (43c). Unexpectedly, even in presence of only 1 equiv. of 43d, with an oxazolidinone
auxiliary, was found to be a good substrate for the aziridination reaction. Resulting in high
yields (Scheme 19 & Table 13). Olefins 43e and 43d afforded products in 60 and 58% yields
respectively. Further, they explored asymmetric reactions by using chiral ammonium salt
catalysts derived from cinchona alkaloids, yielding optically-active aziridines with an
enantiomeric purity of up to 87% ee.
R1 Cl Cbz BTEAC Cbz

+ N N
EWG EWG
Na MeCN, RT R1
43 44 45
Scheme 19. BTEAC catalyzed aziridination of electron-deficient olefins (43) with chloramine- Cbz
(44).
Table 13. Influence of various electron-deficient olefins in the aziridination reactions.
Entry EWG R1 Equiv.a Cat (mol%) Time/h yield (%)

MeO
1 H 2(43b) 20 24 85
O
Ph
2 S
O O
H 2(43c) 20 4 89
O N
3 H 1(43d) 10 4 93
O O
O N
4 Me 2(43e) 10 24 60
O O
O N
5 CO2Et 1(43f) 10 24 58
O O
a
Equiv. of 43
EPOXIDATION
Epoxidation of olefins is one of the most important reactions in organic synthesis as the
epoxides are useful intermediates in the manufacturing of a variety of chemicals. Developing
new catalysts that will utilize environmental friendly oxidants for alkene epoxidation as an
alternative to the stoichiometric oxidation processes still continues to be a subject of interest

[168-170].
Epoxidation of olefins is a classical PTC operation and has been the theme of numerous
synthetic and mechanistic studies in the recent past [171-180]. Kinetic study of ultrasound
assisted phase-transfer catalyzed epoxidation of 1,7-octadiene is greatly enhanced by using a
cocatalyst of phosphotungstic acid in the presence of hydrogen peroxide in an organic
solvent/aqueous solution two-phase medium [61]. The organic-phase reactions, including two
series reactions, are the rate-controlling steps to produce two products, viz., 1,2-epoxy-7-
octene and 1,2,7,8-diepoxyoctane. An active intermediate of the catalyst (Q3PW12(O)nO40,
where Q = R4N+) produced from the reaction of phosphotungstic acid, hydrogen peroxide,
and Aliquat 336.
Aliquat 336 O
O
Phosphotungstate Acid
Hydrogen Peroxide O
47
45 46
(C8H14, A)
(C8H14O, B) (C8H14O, C)
Scheme 20. Epoxidation of 1,7-octadiene under PTC conditions.
For that, a rational mechanism is proposed as follows:
Aqueous Phase
ka,1
nH2O2 + H3PW12O40 H3PW12(O)nO40 + nH2O
ka,2
Q3PW12(O)nO40 + 3HCl H3PW12(O)nO40 + 3QCl
Interface
ka,3
Q3PW12(O)nO40 + H2O Q3PW12(O)n-1O40 + H2O2
kQPWO kQPWO
k1 Q3PW12(O)n-1O40 + C8H14O
Q3PW12(O)nO40 + C8H14
k2
Q3PW12(O)nO40 + C8H14O Q3PW12(O)n-1O40 + C8H14O2
Organic Phase
Scheme 21. Mechanism of epoxidation of 1,7-octadiene under PTC conditions.

where ka,1 = first intrinsic rate constant in the aqueous solution, ka,2 = second intrinsic rate
constant in the aqueous solution, ka,3 = third intrinsic rate constant in the aqueous solution, k1
= first intrinsic rate constant in the organic solution, k2 = second intrinsic rate constant in the
organic solution, kQPW = mass-transfer coefficient of Q3PW12(O)n-1O40, kQPWO = mass-transfer
coefficient of Q3PW12(O)nO40, and n is the number of peroxo oxygen atom with tungsten
metal (W = O) firmed between the reaction of hydrogen peroxide (H2O2) and phosphotungstic
acid (H3PW12O40). Mechanistically, the epoxidation of 1,7-octadiene involves several steps.
First, an active intermediate H3PW12(O)nO40, which is a real oxidant, was formed from the
reaction of phosphotungstic acid and hydrogen peroxide in the aqueous phase. An ion-
exchange reaction that took place between this real oxidant and phase-transfer catalyst to
form the active intermediate of the catalyst Q3PW12(O)nO40 at the interphase between two
phases. Then, this active intermediate of the catalyst Q3PW12(O)nO40, which is organic
soluble, transfers to the organic phase and reacts with the organic-phase reactant (C8H14, A) to
form the epoxides (C8H14O, B and C8H14O2, C).There are many active oxygens for this active
intermediate of the catalyst. However, only one oxygen, providing for the epoxidation,
supplies 1,7-octadiene. Therefore, the active intermediate of the catalyst is reduced to
Q3PW12(O)n-1O40, which can be transferred to the interface for regeneration to produce the
active intermediate of the catalyst. Thus, the overall reaction involves the ion exchange, the
complex reaction in the aqueous phase, the organic-phase reaction, and the mass transfer of
catalyst between two phases. A pseudo steady- state rate law is sufficient to describe the
kinetics of epoxidation of 1,7-octadiene.
We compared the catalytic efficiency of various commercial PTC’s in the
epoxidation of 1,7-octadiene. The quaternary ammonium salts used in this study include
tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride
(TBAC),trioctylmethylammonium chloride (Aliquat 336), tetraethylammonium chloride
(TEAC), and tetrahexylammonium chloride (THAC), (Table 14) .Catalytic activity of these
onium salts indicate that their efficiency in the epoxidation reaction depends primarily on two
factors viz., i) total number of carbons in the salt and reactivity of halides.
The kinetic investigations reveal that those quaternary ammonium salts with larger total
carbon numbers possess higher catalytic reactivity. The main reason is that the organic-phase
reaction is the rate-controlling step. Those larger total carbon number quaternary ammonium
salts, which participate in the formation of the active intermediate of catalyst, prefer to stay in
the organic phase, i.e., the concentration of the active intermediate of catalyst in the organic
phase is increased with an increase in the total carbon numbers of the quaternary ammonium
cations. Hence, almost no reaction occurs in using TEAC as the phase-transfer catalyst in the
epoxidation of 1,7-octadiene in using phosphotungstic acid as the cocatalyst. Aliquat 336 and
THAC have almost the same total number of carbon atoms in the quaternary ammonium
cation. In comparison with the reactivity of these two quaternary ammonium salts, we found
that the reactivity of Aliquat 336 is obviously larger than that of THAC because of the lack of
unsymmetry in the alkyl groups of the quaternary ammonium cation. The steric hindrance for
an unsymmetric quaternary cation is small when it is used to attack the double-bond
compounds. Hence, these quaternary ammonium salts unsymmetric cation possess high
reactivity.
In addition, the order of reactivity of TBAI, TBAB, and TBAC is TBAI > TBAB >
TBAC. Actually, the ion-exchange reaction of Q+(X-) with H3PW12O40 takes place in the
aqueous phase to form a complex that is ready to transfer to the organic phase through the
interface. The order of the selectivity constants K(X-) is K(I-) > K(Br-) > K(Cl-) [121].
Therefore, TBAI exhibits higher reactivity among these three quaternary ammonium salts.
These three quaternary ammonium salts have the same total number of carbon atoms in the
quaternary ammonium cation. However, the iodide ion (I-), which possesses higher activity,
prefers to exchange with the phosphotungstic ion, leading to the formation of the active
intermediate of the catalyst. The two corresponding apparent rate constants, kapp,1 and kapp,2,
are shown in Table X. Obviously, Aliquat 336 possesses higher values of kapp,1 and kapp,2, and
a smaller value of tB,max because of its higher reactivity.
Table 14. Influence of the quaternary ammonium salts on the conversion of 1,7-
octadiene: 35 ml of H2O2 (8%, 9.23 x 10-2 mol), 32 ml of chloroform, 9.09 x 10-3 mol of
1,7-octadiene, 5.77 x 10-4mol mol of quaternary ammonium salt, 1.92 x 10-4 mol of
H3PW12O40, 3.24 x 10-3mol of biphenyl, 50 0C, 1000 rpm, ultrasound conditions (28 kHz,
200 W).
PTC
TEAC TBAC TBAB TBAI THAC Aliquat 336
kapp1 (x 10-3min-1) 0 0.6 0.80 1.31 3.2 20.26
kapp2 (x 10-3 min-1) 0 0.24 0.39 0.72 1.02 8.54
tB,max (min) 2545.25 1752.35 1014.46 524.47 73.71
Further, we examined the role of Aliquat 336 and the H3PW12O40 (cocatalyst) in the
epoxidation of 1,7- octadiene. As shown in Fig. 7, it is found that the conversion of 1,7-
octadiene is low in using sodium tungstate and phosphoric acid as the cocatalyst. In
epoxidation, the conversion of 1,7-octadiene is also low in the absence of Aliquat 336 and
phosphotungstic acid or by individually using each compound. Without the addition of a
cocatalyst, the epoxidation is still low only by hydrogen peroxide oxidation. The active
intermediate of the catalyst H3PW12(O)nO40, which only stays in the aqueous phase, is not
effectively transferred to the organic phase in the absence of Aliquat 336. In contrast, the
reaction is enhanced only in the presence of both Aliquat 336 and the active cocatalyst
H3PW12O40
To examine the influence of ultrasonic irradiation on the conversion of 1,7-octadiene, we
compared the conversion of 1,7-octadiene in silent and ultrasonic conditions. At 120 min,
without ultrasonic irradiation the conversion of 1,7-octadiene is only 76%, but in the presence
of ultrasonic the conversion is 97% and almost 100% for 28 kHz and 40 kHz, respectively.
Selective epoxidation of alkenes (norbornene, cyclohexene, limnone cyclooctene
cyclohexene, styrene and cis-stilbene) with aqueous H2O2 as the oxidant in presence of
Na9[SbW9O33] -methyl tricapryl ammonium chloride system was investigated by Ingle and
Raj under solventless condition [181]. PTC assisted epoxidation of cyclooctene gave only the
epoxide with near quantitative yields, even at ambient temperature conditions and shows no
tendency to undergo allylic oxidation or cleaving of the epoxide like cyclohexene (Table 15).
Epoxidation of cis-stilbene, another activated alkene, gave a mixture of both cis-stilbene
oxide (88% selectivity) and trans-stilbene oxide (balance) as products at the maximum
conversion of the substrate (conversion: 57%). Epoxidation of norbornene and cyclohexene,
at lower substrate: oxidant ratio, resulted in excellent selectivity for the epoxide. However, on
increasing the substrate: oxidant ratio, cyclohexene chiefly underwent allylic oxidation while
norbornene gave norbornanone. Terminal alkenes are normally very less reactive but with this
catalytic system, 1-octene gave a moderate conversion of 38% and showed >99% selectivity
for the epoxide. In the case of limonene, stereoisomers of limonene-1,2-oxide was the only
product obtained.
Figure 7. Effect of the phase-transfer catalyst and cocatalyst on the conversion of 1,7-octadiene: 35 ml
of H2O2 (8%, 9.23 x 10-2 mol), 32 ml of chloroform, 9.09 x 10-3 mol of 1,7-octadiene, 5.77 x 10-4 mol of
Aliquat 336, 1.92 x 10-4 mol of H3PW12O40, 1.44 x 10-3 mol of Na2WO4, 2.88 · 1013 mol of H3PO4,
3.24 x 10-3 mol of biphenyl, 50 0C, 1000 rpm, ultrasound conditions (28 kHz, 200 W).
Hydroxyl-terminated polybutadiene (HTPB) is widely used as fuel binder in composite

solid propellants and adhesives and sealants [182-187]. Wang et al. [188] investigated PTC
assisted epoxidation of hydroxyl-terminated polybutadiene (HTPB) via using H2O2 as the
oxidant and ammonium tungstate hydrate and phosphoric acid as the cocatalysts in an acidic
solution/organic solvent two-phase medium. To explore the influence of Aliquat 336 on the
kinetics of epoxidation of HTPB, the amount of the catalyst was varied at constant amount of
phosphoric acid and ammonium tungstate hydrate. The results indicate that the degree of
epoxidation of HTPB increases from 5.3% to 47.7% with the increase in the amount of
Aliquat 336 up to 0.76 mmol. A further increase in the amount of Aliquat 336 does not
improve the reactivity. This is because of the active catalyst Q3{PO4[W(O)(O2)2]4} (Q+ was
the quaternary cation), which possesses high reactivity to catalyze the epoxidation of olefins.
By using a fixed amount of phosphoric acid and ammonium tungstate hydrate, the amount of
the synthesized active catalyst was also maintained at a fixed value. However a higher
amount of Aliquat 336 does not increase the amount of the active catalyst to enhance the
reactivity. Optimum condition for the reaction was found to be 3:2, the molar ratio of Aliquat
336 to (NH4)5H5[H2-(WO4)6]·H2O).
Table 15. Oxidation of various alkenes over Na9[SbW9O33] + PTC with aqueous H2O2 as
oxidant at different temperatures and different substrate: oxidant ratios.
Entry No. Substrate Sub.:aqu. H2O2 Time (h) Temp. Conv. (%) Selectivity (%)
ratio (0C)
1 Norbornenea 1:1 5 60 5 Norbornene epoxide
(80) norbornanone
(20)
2 Norbornenea 1:2 5 60 5 Norbornene epoxide
(11) norbornanone
(89)
3 Cyclohexene 1:1 6 35 6 Cyclohexene
epoxide (25)
Cyclohexene-2-ol
(41) Cyclohexene-2-
one (34)
4 Cyclohexene 1:0.5 6 35 6 Cyclohexene
epoxide (92)
Cyclohexene diol (8)
5 Cyclooctene 1:1 6 60 6 Cyclooctene epoxide
(>99)
6 Cyclooctene 1:2 9 35 9 Cyclooctene epoxide
(>99)
7 cis-stilbene 1:2 6 60 6 cis-stilbene epoxide
(88) trans-stilbene
epoxide (12)
8 1-Octene 1:2 9 60 9 1-Octene epoxide
(>99)
Reaction conditions—Na9[SbW9O33]: 0.01 mmol, PTC: 0.09 mmol, substrate: catalyst ratio (500:1).
a 1ml toluene was used as solvent
OCH3 OCH3
OCH3 O O
O O O
O O O S
O R
S
N R R
N R
S N R S
O O O O
O O O
O O O
O O
48 49 50
Scheme 22. Methyl α -D-glucopyranoside- (48), methyl α -D-mannopyranoside- (49) and methyl α -D-
altropyranoside-based (50) chiral crown ethers, R = CH2CH2CH2OH.
Mako et al. [189] synthesized various novel, optically active crown ether derivatives
from α-D-altropyranoside (Scheme 22). They investigated the catalytical potential of these
crown ethers by following epoxidation of trans-chalcone with tert-butyl hydroperoxide
(Scheme 23). The investigation revealed a significantly different asymmetric induction by α-

D-glucopyranoside-, α-D-mannopyranoside-, and α-D-altropyranoside-based chiral crown
catalysts. This Indicates the influence of absolute configuration of the crown-ring fused
carbon atoms of the monosaccharides on the enantioselectivity. Molecular modeling
(MCMM) and subsequent DFT calculations indicate that the use of mannopyranoside based
crown ether (49) and that of glucopyranoside-based catalyst (48) results in the preferred
formation of the opposite antipodes of the corresponding epoxyketone. In contrast, when
altropyranoside-based crown (50) is employed as catalyst, practically no asymmetric
induction was noticed.
O O
O H
catalyst, t-BuOOH H
toluene, aq.20%NaOH
51 52
Scheme 23. Epoxidation of trans-chalcone with tert-butyl hydroperoxide using novel, optically active
crown ether (50) as catalyst.
Recently, epoxidation of substituted chalcones and chalcone analogues (53) with tert-
butylhydroperoxide catalyzed by the chiral monoaza-15-crown-5 lariat ethers annellated to
methyl-4,6-O-benzylidene-α-D-glucopyranoside- or mannopyranoside have been investigated
[190] and the results indicates significant asymmetric induction (Scheme 24). Also the study
explains the importance of the position of the substituents in the aromatic ring of the chalcone
on the chemical yields and enantiomeric excesses. The lowest enantioselectivities were
obtained in the case of ortho-substituted model compounds and the highest ee values were
found in the case of para-substituted models ortho-substituted model compounds (Table 16).
O
O O
catalyst, t-BuOOH Ar' S
Ar' R
toluene, aq.20%NaOH
53 54
Scheme 24. Epoxidation of substituted chalcones with tert-butyl hydroperoxide using crown catalyst.
Chalcones with electron- donating methyl-substituent afforded products 54b–d in better

yields (72–90%) and the ee values increased according to the position of methyl group (71%,
87%, and 92%, respectively) (Table 16, entries 2–4). Authors reported a similar trend in the
case of methoxy-substituents 54e-g. In the presence of catalyst 1, the yields were 58–77%,
while the ee values were in the range of 84–95% (Table 16, entries 5-7). In the chlorophenyl
epoxyketones cases, the products 54h-k were obtained in 65–71% yields and the ee values
increased according to the position of the chloro-substituent: the 2-chlorophenyl-, 3-
chlorophenyl-, and 4-chlorophenyl products were obtained in an ee of 69%, 79%, and 97%,
respectively (Table 16, entries 8–10).Epoxidation of chalcones with electron-withdrawing

nitrosubstitutent afforded epoxyketones 54l-n in 55–66% yield with high (80–99%) ee
values(Table 16, entries 11–13).The substituents close to the reaction center prevent the
asymmetric induction, hence the further the substituents are placed from the reaction center,
the higher the extent of enantioselectivity.
Table 16. Effect of substituents in chalcone on the asymmetric epoxidation in the

presence of chiral crown ether 1 at 0–2 0C.
Entry Product Ar’ Time(h) Yield (%) ee (%)

1 54a Ph 1 82 94
2 54b 2-CH3-Ph 4 72 71
3 54c 3-CH3-Ph 2 90 87
4 54d 4-CH3-Ph 2 81 92
5 54e 2-CH3O-Ph 8 69 84
6 54f 3-CH3O-Ph 2 77 88
7 54g 4-CH3O-Ph 3 58 95
8 54h 2-Cl-Ph 3 65 69
9 54i 3-Cl-Ph 2 68 79
10 54k 4-Cl-Ph 2 71 97
11 54l 2-NO2-Ph 1 66 80
12 54m 3-NO2-Ph 1 55 >99
13 54n 4-NO2-Ph 2 63 96
The ultrasound irradiation assisted epoxidation [191] of chalcones with aqueous sodium
hypochlorite catalyzed by benzyldimethyltetradecyl ammonium chloride afforded 2,3-epoxyl-
1,3-diaryl-1-propanones in good yield. On increasing the temperature to 30–34 0C or 40–44
0
C, the yield of epoxidation of benzalacetophenone increases to 79% and 83%, respectively
(Entries 2 & 3; Table 17). In the absence of PTC, only 6% yield was observed (Entry 4; Table
17). On increasing the amount of benzyldimethyltetradecyl ammonium chloride from 0.025
mol equivalent catalyst to 0.05 mol equivalent, the yield of epoxide increases from 84%
(Entry 5; Table 16); to 93% (Entry 6; Table 17).
Table 17. Influence of temperature and catalyst concentration on the epoxidation of

benzalacetophenone with sodium hypochlorite catalyzed by PTC under ultrasound
irradiationa.
Entry Amount of Substrate/NaClO(mol) Temperature Yield(%)
PTC(mmol)
1 0.05 1:1.5 22-26 48
2 0.05 1:1.5 30-34 79
3 0.05 1:1.5 40-44 83
4 0 1:1.8 40-44 6
5 0.025 1:1.8 40-44 84
6 0.05 1:1.8 40-44 93
a- Reaction time: 2 h.
ESTERFICATION
In last decade, a great number of esters have been synthesized using the phase transfer
catalysis methodology [192-202]. Yang and Peng [203] reported the esterification of sodium
salicylate to synthesize butyl salicylate catalyzed by TBPB under ultrasound irradiation in a
continuous two-phase-flow reactor. They investigated the effects of power and frequency of
ultrasound on the third-liquid catalyzed esterification (Table 18). The product yields were
65.1% (silent, kapp = 0.0112 min-1), 78.2% (300 W, 28 kHz, kapp = 0.0215 min-1), 71.5% (300
W, 40 kHz, kapp = 0.0150 min-1), 71.2% (300 W, 50 kHz, kapp = 0.0148 min-1) and 69.3% (300
W, 80 kHz, kapp = 0.0135 min-1), decreasing with the increase of ultrasonic frequency. The
higher frequency resulted in a larger sonic resistance and loss of energy during the sonic
waves propagating through the medium. The effect of power of ultrasound on the reaction
was performed at a frequency of 28 kHz. At 200 W, the kapp was found to be 0.0139 min-1; at
100 W the kapp was found to be 0.0108 min-1A high power of ultrasound offers much energy
into the medium to enhance the reaction.
PTC methodologies are used to activate carboxylate nucleophiles for the purpose of
preparing ester derivatives of brominated poly (isobutylene-co-isoprene) (BIIR). TBAB plays
a dual catalytic role in PTC esterifications of BIIR by rendering carboxylate anions
nucleophilic and by isomerising exoallylic bromide into more reactive BrMe electrophiles
[204]. The sensitivity of reaction rates to TBAB concentration is examined by the authors.
The initial reaction rate generated by 0.1 equiv. catalyst was improved by a factor of 2.4 on
increasing the catalyst loading to 0.75 equiv and by a factor of only 2.8 when 1.5 equiv of
TBAB was employed. The results reveal that catalytic amounts of the catalysts do support an
efficient process and that higher levels have a relatively small effect on reaction velocities.
Knowledge of reaction fundamentals are used to prepare copolymers from BIIR and
carboxylate-terminated polybutadiene (cBR) that phase-partition in the manner required for
blend compatibilization applications.
Table 18. Effect of ultrasonic frequency and power on the esterfication of sodium
salicylate.
Entry No. Power Frequency(kHz) Product Yielda in kapp(10-2 min-1)

(W) organic exit (%)
1 0 0 65.1 1.12
2 300 28 78.2 2.15
3 300 40 71.5 1.50
4 300 50 71.2 1.48
5 300 80 69.3 1.35
6 100 28 64.3 1.08
7 200 28 69.8 1.39
An environment friendly method was developed for the alkylating esterification of 1-

hydroxy-3-phospholene oxides under solventless, phase transfer catalytic, and MW
conditions [205]. The MW-promoted alkylations were carried out in solid–liquid phase in the
presence of 1 equiv. of potassium carbonate, in the absence of any solvent at 100 0C using
different alkylating agents viz., benzyl bromide, ethyl iodide, n-propyl bromide, isopropyl
bromide and n-butyl bromide (Scheme 23).
K2CO3/TEBAC
+
P RX MW, 100 0C P
HO O RO O
55 56
X= Br, I
R=Bn(a) Et(b), nPr(c), iPr(d), nBu(e).
Scheme 25. Esterification of 1-hydroxy-3-phospholene oxides under solventless, phase transfer

catalytic and MW conditions.
Table 19. Esterification of 1-Hydroxy-3-methyl-3-phospholene 1-Oxide (55) by

alkylation at 100 C in the presence of K2CO3.
Entry No. RX TEBAC Mode of Irradiating Yield (%)

Heating Time/Heating
Time(Hours)
n
1 PrBr - MW 1b 73
2 EtI 5% MW 1b 90
3 EtI - MW 1b 80
n
4 PrBr 5% MW 1b,c 94
i
5 PrBr - MW 1.5d 42
i
6 PrBr 5% MW 1b 65
n
7 BuBr - MW 1b 69
n
8 BuBr 5% MW 1b,c 96
9 BnBr - MW 1b,c 92
10 BnBr 5% MW 1b,c 94
n
11 BuBr - Δa 1b 64
n
12 BuBr 5% Δa 1b,c 89
13 BnBr - Δa 1b,c 85
14 BnBr 5% Δa 1b,c 87
aThermal heating.
In the absence of triethylbenzylammonium chloride (TEBAC), the ethyl (56a), n-propyl

(56b), n-butyl (56d), and benzyl (56e) esters were obtained in 80, 73, 69, and 92% yield,
respectively, (Table 19, entries 1, 3, 7, and 9). However in the presence of 5% of TEBAC, all
reactions went to completion and the yields were, in the above order, 90, 94, 96, and 94%,
respectively (Table 19, entries 2, 4, 8, and 10). The authors reported that except in the case of
benzyl bromide, the yields were significantly higher in the presence of 5% of TEBAC. Thus,
the esterfication with reagents of normal reactivity may be promoted by the use of TEBAC.
Further, for comparison purpose, some of the above reactions were also carried out under
thermal conditions. Uncatalyzed thermal reaction of hydroxyphospholene oxide with n-butyl
bromide and benzyl bromide, esters 56d-e were obtained after 1 h in 64 and 85%,
respectively (Table 19, entries 11 and 13). On the other hand, in the presence of 5% of
TEBAC, both alkylations were essentially completed as the isolated yields were 89 and 87%,
respectively (Table 19, entries 12 and 14). The MW-promoted esterifications were more
efficient than the thermal variations, resulting in improved yields (5–7%) (Table 19, entries 7
vs. 11, 8 vs. 12, 9 vs. 13, and 10 vs. 14).
CONCLUSION
Nowadays, PTC catalyzed reactions belong in the toolbox of each synthetic organic
chemist and have been used in many fields of organic synthesis leading to products of various
interests. Still there is an urge in their minds to find more and more methods that augment
their catalytic activity. This can be achieved by optimizing reaction conditions by the use of
ingenious new analytical techniques viz., ultrasound and microwave irradiation, or by the use
onium salts with multi active sites. We have presented in this chapter some recent trends in
the PTC catalyzed reactions viz., the alkylation reactions, Heck reaction, aziridine reaction,
epoxidation and esterfication that highlight the efforts and interest in developing more
efficient processes according to the new requirements of the chemistry of the 21st century.
Ingenious new analytical and experimental techniques in conjunction with PTC have been
compared with conventional PTC techniques. The comparison is very encouraging for future
applications of these techniques in conjunction with PTC. The salient advantages of this green
technology are easily recognized in the examples given. The chapter supports the growing
importance shown by researchers for highly active onium salts with multiple number of
active-sites. A vast array of experimental parameter’s, viz., substrates, catalytic system, bases,
temperature, solvent, ultrasonic frequency and microwave power, influence on optimum
reaction conditions have been outlined. Special features and mechanistic aspects are presented
which helps us in understanding the practical value of this catalytic methodology. The
development of PTC process in conjunction with various types of technologies delivers not
only higher reactivity and stereoselectivity but also new synthetic opportunities, expanding
the applicability of phase-transfer catalysis in modern organic synthesis. At present, the
kinetic details of many PTC in conjunction with microwave/ultrasonic assisted reactions
remain obscure. Improvements in reaction kinetics are expected with the advent of more
systematic kinetic studies under these PTC conditions. Due to continuous improvements
brought about by the advancements in the PTC technology, it can be predicted that how
practical applications of PTC’s can be further expanded in the future. However, continuous
growth of PTC can be accelerated further only by the practicing chemists who will use the
same brilliance and creativity that is the long tradition of catalysis and use it with the new
perspective for transformative innovations for sustainability.
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Chapter 11
HEXENOIC ACIDS AND THEIR DERIVATIVES –

PREPARATION USING SELECTIVE
HOMOGENEOUS CATALYSTS
Libor Červený and Eliška Leitmannová

Institute of Chemical Technology, Departement of Organic Technology,
Czech Republic
INTRODUCTION
Some C6 unsaturated alcohols, aldehydes and acids are widely used in perfume
chemistry. The easiest method for the preparation of hexenoic acids from the point of view of
selectivity and simplicity is the selective hydrogenation of easily available sorbic acid
(trans,trans-hex-2,4-dienoic acid). Depending on the catalyst used different regio and
stereoisomers, can be obtained in various mixtures.
From hexenoic alcohols the most commonly used compounds of this type are the so-
called “leaf alcohols”, specifically cis-hex-3-en-1-ol and trans-hex-2-en-1-ol. These
compounds can be prepared by selective hydrogenation of the sorbic alcohol obtained for
example from the chemical reduction of sorbic acid.
Details of the preparation of these compounds by hydrogenation using heterogeneous
catalysts are given elsewhere [1-4]. The major disadvantages of the use of heterogeneous
catalysts in this case are the low selectivity of the process (in the case of hex-3-enoic acid
derivatives there is essentially no selectivity) and the use of sorbic acid itself is impossible.
Instead salts or preferably methyl or ethyl esters are used, introducing another step to the
process. The use of homogeneous catalysts opened new possibilities to carry out the
hydrogenations and significantly higher selectivities of formation of the desired products.
As stated above hexenoic acids and alcohols have very interesting fragrant properties.
The titling of the two hexenols as leaf alcohols is partly reflective of their smell – their
fragrance resembles that of freshly cut grass. Perfumers [5] define their fragrance a little more
precisely: cis-hex-3-en-1-ol is specified by its intense smell of fresh grass, it is a component
of geraniol, lavender and brandy mint oil, it is added to flower aromas (lilac for example) and
372 Libor Červený and Eliška Leitmannová
it can be used in imitations of mint and different fruit mixtures. trans-Hex-2-en-1-ol has in
low notes a strong fruit smell (chrysanthemum or wine), it is sweeter and more fruity than cis-
hex-3-en-1-ol and it is often used as a component of artificial strawberry. It is also used for a
refreshing orange aroma and it is a component of artificial geraniol and lavender oil. trans-
Hex-2-en-1-oic acid has a warm fruit aroma after dilution, partly herbaceous and slightly
acidic. It is used as an imitation of raspberry or in many other fruit aromas that require a
caramel-acid note.
The fragrant properties of hexenoic aldehydes are also very interesting for the perfume
industry but the simplest method of preparation (aldol condensation) was not superseded by
hydrogenation due to the low stability of aldehydes.
HOMOGENEOUS HYDROGENATION OF SORBIC

ACID AND ITS DERIVATIVES
The homogeneous hydrogenation of sorbic acid and its derivatives can be defined by the
position at which the hydrogen addition occurs. The addition of hydrogen at positions 2, 3 or
4 to the one of the double bonds of sorbic acid is defined as regioselective hydrogenation. In
this type of reaction the trans configuration of the other double bond is preserved. When the
hydrogen is added to positions 2 and 5 (generally called 1, 4 addition) both the cis and trans
isomers can be formed. If in this reaction one of the isomers is formed preferentially the
reaction is described as stereoselective hydrogenation.
The following chapters detail the progress in the development of homogeneous
organometallic catalysts for the selective hydrogenation of sorbic acid and its derivatives
(esters, alcohols, salts).
ORGANOMETALLIC COMPLEXES BASED ON COBALT

The first homogeneous catalyst used for the hydrogenation of sorbic acid [6],[7] was
K3[Co(CN)5]. The reaction was carried out at room temperature with a hydrogen pressure of
0.1 MPa at a 3.3:1 substrate: catalyst ratio in aqueous solution. Sorbic acid was added as its
K+ salt and was selectively hydrogenated to the corresponding salt of trans-hex-2-enoic acid.
In subsequent work [8] the selectivity was more precisely specified. The ratio of hexenoic
acids was determined using gas chromatography. With water as a solvent the ratio of trans-
hex-2- : trans-hex-3- : trans-hex-4-enoic acid was 82 : 17 : 1. In methanol the selectivity to
trans-hex-2-enoic acid was higher, up to 95 %. The active species of the catalyst was the
hydride [CoIII(CN)3H]3-. The authors of this work proposed that the hydrogen is not
transferred in pairs and the π-coordination of the olefin is not realized before hydrogen
transfer. Synchronic formation of both 2- and hex-3-enoic acid was accounted for by
rearrangement of the intermediate [9]. The mechanism of the reaction is shown in Figure 1.
Hexenoic Acids and Their Derivatives 373
X
[Co(CN)5H]3- +
H
X X
X
3- 3-
3- Co(CN)5 Co(CN)5
Co(CN)5
H H
X X
H H
Figure 1. Hydrogenation[9] of dienes using [CoIII(CN)5H]3.
Selectivity to trans-hex-2-enoate was slowly decreased using natrium sorbate in the

hydrogenation. Another step was to determine the effect of phase transfer compounds on the
course of the reaction [10]. In the absence of a phase transfer compound the selectivity to
trans-methyl-hex-2-enoate (hydrogenation of methylsorbate) was 90 %. In the presence of
polyethyleneglycol (phase transfer compound) the selectivity decreased to 81 %. In a two-
phase water-dichloromethane system methyl-trans-2-enoate and trans-hex-3-enoate were
formed in a 65:35 ratio. When benzyltriethylammoniumchloride was added to this system the
proportion of trans-hex-3-enoate formed was increased to 75 %. The differences in the
behavior of the reactions are probably a result of the different media in which the reactions
occur [11]. Without phase transfer compounds the reaction takes place in the aqueous phase,
in contrast when tetraalkylamonium compounds are present complexes such as [R4N]3
[Co(CN)5H] are formed and these are soluble in organic solvents. Due to this fact
hydrogenation reactions in the presence of benzyltriethylammonium chloride take place in the
organic phase. Sorbic acid was not hydrogenated under the chosen reaction conditions (room
temperature, 0.1 MPa).
A similar result was obtained by Alper [12] for the hydrogenation of potassium sorbate
using similar conditions with a different phase transfer compound (beta-cyclodextrine). This
author obtained yields for trans-hex-2- and trans-hex-3-enoate of 75% and 13 % respectively.
ORGANOMETALLIC COMPLEXES BASED ON RHODIUM

The investigations into the use of complexes based on cobalt were followed by the
examination of different Rh complexes. For the hydrogenation of sorbic acid a series of
different Rh complexes was tested [13] at room temperature with a hydrogen pressure of
0.3 Pa in basic solution. Using Wilkinson´s catalyst [RhCl(PPh3)3] even at low conversion
only saturated hexanoic acid was formed. On the other hand using [RhCl (PPh3)2
(Ph2PO2CCH=CMe2)] a mixture containing 52 % of hex-4-enoic acid and 48 % of hexanoic
acid was obtained after total conversion of sorbic acid. In addition this complex was more
active than Wilkison´s catalyst.
Another Rh catalyst used [14] was [H2RhIII(Ph2N3)2(PPh3)2]. At a hydrogen pressure of

0.1 MPa and a temperature of 30 – 40 °C with DMSO as the solvent trans-hex-2-enoic acid
with a small amount of trans-hex-3-enoic acid was obtained. Using temperatures higher than
50 °C trans-hex-2-enoic acid was subsequently hydrogenated to hexanoic acid after the total
conversion of sorbic acid. When other solvents were used the catalyst was significantly less
active and selective.
ORGANOMETALLIC COMPLEXES BASED ON CHROMIUM

The hydrogenation of methyl sorbate to methyl-cis-hex-3-enoate was enabled [15] using
complexes of the types [Cr(CO)3], [Cr(CO)6], [W(CO)3] and [(arene)Cr(CO)3]. Reactions
were carried out at temperatures of 150 - 165 °C, a hydrogen pressure of 4.8 MPa and a
catalyst : substrate ratio of 1 : 9. The activity of the different complexes differs significantly
depending on the ligand whereas selectivity was almost unaffected by the type of ligand. The
authors detailed the results obtained through the comparison of different arene ligands. In
cyclohexane solution the benzene complex showed the lowest activity (TOF = 2.4 h-1 at
165 °C). The highest activity (at 150 °C) was obtained using the complex with 3-
carbomethoxyanisol as an arene ligand. The obtained values of selectivity were from 91.8 to
98.9 % of methyl-cis-hex-3-enoate. In this work [15] it was found that the arene group is not
necessary for this reaction as the complex [(cycloheptatriene)Cr(CO)3] showed a higher
activity than the complexes [(aren)Cr(CO)3]. This demonstrates that the hydrogen was
transferred directly to carbon atoms 2 and 5 of methylsorbate. The reaction path including
1,2-addition of hydrogen and the consecutive isomerisation was therefore eliminated. Based
on these results the reaction mechanism generally accepted to date was formulated (Figure 2).
The initial step of the catalysis is the dissociation of the arene ligand from the Cr complex
followed by the formation of the coordinately unsaturated species [Cr(CO)3].
H2 R X
X
R H Cr H R X
Cr(CO3)Y H H
CO CO
CO
1
Figure 2. Diene hydrogenation[15] using [(arene)Cr(CO)3] complexes S = solvent (THF, acetone), X =

CO2Me, Y = arene.
During the study of the influence of the arene substituents on the structure and activity of
the catalyst it was found that electron accepting substituents accelerate the catalytic reaction
while electron donating groups significantly decrease the activity of the catalyst [16]. As a
model reaction for the study of this phenomenon the hydrogenation of methyl sorbate to
methyl-cis-hex-3-enoate was used. As stated above almost no influence on selectivity was
observed and for almost all the catalysts with different substituents 100 % selectivity to
desired methyl-cis-hex-3-enoate was obtained. The hydrogenations were performed in THF
for 5 hours (6 MPa H2, 120°C).
It was demonstrated that the simple dissociation of the arene ligands from chromium
resulted in higher activity of the catalyst. A comparison [17], of the arene complexes showed
that a longer bond length between chromium and the carbon atoms of the arene ligand
correlated with increased dissociation. In [(1,2,3-trimethoxybenzene)Cr(CO)3] the plane [18]
formed from C-atoms of the ring was significantly deformed and this complex was active
even at a temperature of 80°C. This phenomenon was more evident in Cr-carbonyl complexes
of the polyaromatic compounds like naphtalene, anthracene or phenanthrene. To date the
most active compound was [(naphtalen)Cr(CO)3] that stereoselectively catalyzed
hydrogenation [19] of methylsorbate at a temperature of 30 °C and a hydrogen pressure of
0.1 MPa. The cause [20] of such high activity is probably the solvatation of the naphtalene
complex in THF, forming [(THF)3Cr(CO)3]. In recent work a Cr complex with similarly high
activity was prepared by Kündig [21]. The author prepared the η2-methylacrylate complex
[(C6H6)Cr{CH2CH(CO2CH3)}] that catalyzed the hydrogenation of methylsorbate at room
temperature and 0.1 MPa.
The stereoselective hydrogenation of conjugated dienes using chromium catalysts is not
limited to the hydrogenation of methylsorbate but was also used [17] for the synthesis of
many other natural compounds. During these syntheses it was found that the reaction can be
applied to molecules containing many different functional groups (non-conjugated double
bonds, esters, ketones and carboxylic acids). Using some of these the Cr catalyst was
successfully heterogenized [22] by mixing chromium hexacarbonyl with polystyrene.
Heterogenization was accomplished by linking the Cr(CO)3 groups to the phenyl ring of
polystyrene. The heterogeneous Cr catalyst had lower activity in comparison with
[(aren)Cr(CO)3] complexes but had similar selectivity. The catalyst could be reused with no
loss of selectivity. Unfortunately the attempt to reproduce the described heterogenization
method followed by hydrogenation was not successful [23]. Using all the described
heterogenized Cr catalysts very high leaching was observed and catalysts lost their activity
after reuse.
Furuhata [24] used 1,4-hydrogenation for the direct synthesis of cis-hex-3-en-1-ol from
hexa-2,4-diene-1-ol. A temperature of 190 °C and a hydrogen pressure of 5 MPa were
necessary for reactions using all the [(arene)Cr(CO)3] complexes. The catalyst : substrate
ratio was 1 : 20 and the desired cis-hex-3-en-1-ol was obtained with 96 % selectivity and TOF
= 5 h-1.
The direct 1,4-hydrogenation of sorbic acid using Cr complexes as catalysts failed. Sorbic
acid and its potassium salt were hydrogenated [25] at 160 - 180 °C and 5 MPa using
chromium hexacarbonyl as the catalyst; a mixture of cis-, trans-hex-3-enoic and trans-hex-2-
enoic acids with trans-hex-2-enoic acid as the major component was obtained.
In spite of their high selectivity, hydrogenations using chromium hexacarbonyl and
[(aren)Cr(CO)3] complexes as catalysts have many disadvantages. From these disadvantages
the main is toxicity of chromium carbonyl compounds, than high catalyst : substrate ratios .
The problem is also that the industrial use of homogeneous Cr catalysts is not described and
the reactions with heterogenized catalysts were not reproducible. And finally the
stereoselective hydrogenation of sorbic acid itself is not possible.
ORGANOMETALLIC COMPLEXES BASED ON RUTHENIUM

Heinen [26] synthesized a water soluble complex of ruthenium [RuCl2{P(CH2)3OH}]2
that catalyzed the hydrogenation of sorbic acid to trans-hex-4-enoic acid with 82 %
selectivity in a two-phase water-ethylacetate system. When the reaction was carried out in a
one-phase system (water) the selectivity was only 62 % and the rest of the mixture was
composed of hexanoic acid. The increase in the selectivity for the desired product in the two-
phase system was probably due to the extraction of the primary (unsaturated) products of the
reaction into the organic phase and the resulting shift of the equilibrium.
The alternative to Cr catalysts mentioned above (preparation of cis-hex-3-enoic acid) was
also developed by Heinen [27]. The water soluble [Cp*RuCl(CO){P((CH2)3OH)3}] complex
catalyzed the hydrogenation of sorbic acid at 80 °C and 5 MPa in a two-phase water-heptane
system with 66 % selectivity to cis-hex-3-enoic acid. At 62 % conversion the reaction rate
determined by TOF was 15.5 h-1. The main undesired product was saturated hexanoic acid,
which was formed with 22 % selectivity. The stereoselective hydrogenation of sorbic alcohol
was not possible using this complex.
A particularly suitable catalyst for this reaction appeared [27] to be the cationic
[Cp*Ru(MeCN)3]+ complex (the counter ion was triflate (Tf)). After the dissociation of the
acetonitrile ligands and the addition of the diene a similar complex to the Cr systems was
formed. When the reaction took place in a two-phase system with water as one of the phases
strong leaching of the catalyst to the nonpolar phase was observed. A highly active catalytic
system (80 °C, 5 MPa) producing cis-hex-3-enoic acid with 67 % selectivity was obtained.
The selectivity was strongly dependent on the conversion due to the isomeric activity of the
system. When the catalyst was used for different sorbic acid derivatives the selectivity was
strongly dependent on the dienic system. Sorbic alcohol was hydrogenated with 82 %
selectivity (total conversion) to cis-hex-3-en-1-ol, the hydrogenation of sorbic aldehyde
produced a mixture of hexenals. A further development was the use of a two-phase system
with nitromethane as a polar phase; in this case the catalyst remained in the nitromethane
phase in contrast with water as polar phase. Sorbic acid and its ethyl ester were hydrogenated
in a two-phase nitromethane – heptane system to cis-hex-3-enoic acid with 75 % selectivity or
to ethyl-cis-hex-3-enoate with with 84 % selectivity. Using a hydrogen pressure of 5 MPa the
TOF of sorbic acid was 15 h-1 and that of ethyl sorbate was 18 h-1 at 60 °C. This catalytic
system had [27] some disadvantages, namely low activity, selectivity of only up to 90 % and
the impossibility of the use of nitrormethane as an industrial solvent as it is explosive at
higher temperatures.
Due to the absence of other ligands in the [Cp*Ru(MeCN)3]Tf complex it was deduced
that the high selectivity probably results solely from the cationic RuCp* fragment. As a result
the following reaction mechanism was proposed [28] (figure 3).
The acetonitrile ligands dissociate stepwise from the catalyst and the molecule of sorbic
acid is simultaneously added through its C=C double bonds. The addition of the dienic system
where the diene is in the cis-conformation was proved by Mashima [29] based on the
complexation reaction of (E,E,E,E)-1,8-diphenyl-1,3,5,7-octatetraene with [Cp*RuCl]4. The
Cp*Ru(diene) complexes described by Fagan [30] contain the diene in the cis-conformation.
After the π –complex formation with sorbic acid the oxidative addition of one molecule of
hydrogen takes place. In this newly formed complex the positions 2 and 5 in the molecule of
sorbic acid are angled directly towards the hydride ligands and the transfer of hydrogen to
these positions is very probable. In the final step of the catalytic cycle the cis-hex-3-enoic
acid dissociates from the Ru center and the solvated Cp*Ru complex is free for the addition
of a new molecule of sorbic acid. One face of the active center is blocked by the Cp* ligand
and the other is available for reaction with the substrate molecules.
CF3SO3-
Ru
MeCN NCMe
MeCN
+
Tf -
Ru +sorbic acid
S
- kys. cis-3-hexenová S - 2S
- cis-hex-3-enoic acid S + kyselina sorbová
+S -2S
+S
+
Tf - +
Tf -
S Ru S
Ru S
COOH
COOH
+ + H2
+2S
Tf - -S
Ru H
H
COOH
Figure 3. Postulated mechanism[28] of sorbic acid hydrogenation to cis-hex-3-enoic acid (S = solvent).
This was the reason for the synthesis [28],[31],[32] of the model Cp*Ru complexes i.e.
[Cp*Ru(η4-MeCH=CHCH=CHCO2H)]+X- (X- = CF3SO3- or [B{C6H3(CF3)2-3,5}4]- (BARF)),
that are were efficient complexes for the hydrogenation of sorbic acid to cis-hex-3-enoic acid
and of sorbic alcohol to cis-hex-3-en-1-ol (leaf alcohol) under mild conditions using a two-
phase liquid system.
Complexes were obtained as orange powder or crystals with yields of 72 % and 41 %
respectively. The first of the complexes is soluble in polar solvents such as alcohols,
nitromethane or sulfolane and is insoluble in nonpolar solvents such as ethers or alkanes. It
can be used as a catalyst in liquid two-phase systems including nitromethane-dibuthylether,
ethyleneglycol-MTBE or sulfolane-MTBE where the complex remains in the polar phase.
After the reaction the catalyst can be simply separated by decantation. At 60 °C the solvents
in the nitromethane-dibutylether and sulfolane-MTBE systems become soluble but at room
temperature they are insoluble. The results obtained showed that the “naked” [Cp*Ru]+
particle is more active than the Ru catalysts used previously. To prove the reaction
mechanism shown in Figure 3, a spectroscopic study of the hydrogenation was carried [33]
out. It was found that the hydrogen was placed solely in positions 2 and 5 in sorbic acid
molecule. On the both of the methylene groups of cis-hex-3-enoic acid exactly one proton
was present (assigned by 1H-NMR).
In subsequent work [34] the most selective catalyst was used in a two-phase system with
MTBE and dibutylether as the non-polar product phase and the ionic liquid Bmim PF6 (1-n-
butyl-3-methylimidazolium hexafluorophosphate) as the polar catalyst phase. In this system
the activity of the catalyst was significantly higher in comparison with the system used
previously (TOF up to 1100 h-1) but the selectivity to cis-hex-3-enoic acid was lower.
Catalysts of the type [Cp*Ru (diene)]+X- can be used [35] for the hydrogenation of
different dienes to their cis-unsaturated forms. The author used sorbic acid and sorbic alcohol
and also cyclooctadiene. For the hydrogenation of sorbic aldehyde this type of catalyst is not
applicable due to its deactivation by the aldehyde itself. Modifications of the counterion X-
were also tested as was the modification of the other ligand of the
pentamethylcyclopentadiene complex by exchange with indenyl or fluorenyl. The catalysts
obtained by these modifications can catalyze the hydrogenation of the chosen dienes with
high selectivity and activity.
The mechanism of the hydrogenation of different hexadiene compounds (acid or alcohol)
was studied. It was confirmed [36] that the mechanism forming the desired product proceeded
in accordance with the scheme shown above (Figure 3) but the reaction of the desired product
with the Ru center to form of undesired side products was different for the both of the
compounds. In the case of sorbic acid the undesired side products are the other hexenoic
acids; in the case of sorbic alcohol the undesired side products are hemiacetals or acetals
respectively. In the sorbic acid hydrogenation it was found that the monounsaturated acid
formed could also interact with the Ru active particle (π-electrons of C=C double bond and
C=O carbonyl group) and hydrogenation does not stop at the desired cis-hex-3-enoic acid and
the final product could be hexanoic acid. The undesired side products (other isomers of
hexenoic acids) are formed by isomerisation on the active center. In the sorbic alcohol
hydrogenation this reaction did not occur [37]. The undesired hemiacetals are formed due to
the migration of the double bond on the chain forming the unstable monounsaturated
aldehydes and by the reaction of these compounds with the alcohols present in the reaction.
No saturated hexanol was detected in the mixture.
Methyl and butyl esters of sorbic acid were also hydrogenated [38] using the optimal
catalyst and a higher selectivity to the desired cis-unsaturated product was observed due to the
decrease in electron density.
The catalysts of the type [Cp*Ru (diene)]+X- can not only be used in two-phase or
homogeneous systems as the immobilization of these catalysts was also successfully
performed. Two types of heterogenization were tested – at first the immobilisation using
hydrogen binding [39] through the oxygen of the triflate ion. This interaction is nonbonding
and no effect on selectivity was expected (this was confirmed in the sorbic acid
hydrogenation; in the sorbic alcohol hydrogenation the selectivity was marginally lower due
to the synergic effect). The second type of immobilization tested was using ionic exchange
[40] of Na cations of different anionic clays with the cation of the active complex. This type
of immobilization did not affect the selectivity and the catalyst could be reused with no loss
of selectivity and minimal loss of activity.
PREPARATION AND PROPERTIES OF [CP*RU (DIENE)]+CF3SO3

The optimal preparation of the catalyst is described in the patent [35]. 0.023 g of
[Cp*RuCl2]n (0.08 mmol) was dissolved in diethylether (5 ml) with an excess of sorbic acid
(1.3 mmol)(or another hydrogenated diene), zinc powder (2.3 mmol) and silver triflate (0.1
mmol). The mixture was stirred for 2.5 hour at ambient conditions. An orange solution was
formed and after solvent evaporation and purification [Cp*Ru(sorbic acid)]CF3SO3
(0.08 mmol)was obtained as a powder.
The prepared catalyst is soluble in polar solvents and slightly soluble in ethers. In the
polar solvents fast degradation of the complex was observed (the solution quickly became
brown). When alcohols were used as solvents it was found that longer carbon chains in the
alcohols resulted in lower solubility of the complex and slower catalyst degradation. Water is
a catalytic poison and causes catalyst deactivation. Air humidity causes slow catalyst
deactivation and it is possible to store the catalyst in air for 24 hours with no loss of catalytic
properties.
The use of polar solvents results in the formation of strong (binding) interactions with the
complex. Interactions with the Ru center could be formed by the free electron pairs [38] and
saturation of the complex may occur in the first step (16 e- to 18 e-). The second step could be
total solvatation (Figure 4) of the complex resulting in the formation of the clusters
(Figure 5).
+
Tf - +
Ru S Tf -
COOH Ru S
S S
Figure 4. Possible solvatation of the catalyst[38] (S =solvent).
+
Tf - Tf -
+ Ru S
S S S
Ru
Ru
S S S
S Ru +
Tf -
Tf -
+
Figure 5. One of the possible cluster.

Table 1. Summary of the catalysts used for the hydrogenation of C6-dienic compounds
Catalyst Substrate Product Sel. (%) Arrangement Lit.

K3[Co(CN)5] Potassium Potassium trans-hex-2- 82 - 95 Homogeneous [6]- [8]
sorbate enoate
K3[Co(CN)5] Methylsorbate Methyl-trans-hex-2- 90 Homogeneous [10]
enoate
K3[Co(CN)5] Methylsorbate Methyl-trans-hex-2- 65 Two-phase [11]
enoate
K3[Co(CN)5] Methylsorbate Methyl-trans-hex-3- 75 Two-phase (+ [12]
enoate phase transfer
compound)
[RhCl(PPh3)2(Ph2PO2CCH= Sorbic acid trans-Hex-4-enoic acid 52 Homogeneous [13]
CMe2)]
[H2RhIII(Ph2N3)2(PPh3)2] Sorbic acid trans-Hex-2-enoic acid 90 Homogeneous [14]
[(aren)Cr(CO)3] Methylsorbate Methyl-cis-hex-3-enoate 92-99 Homogeneous [15]
[19]
[(aren)Cr(CO)3] Sorbic alcohol cis-Hex-3-en-1-ol 96 Homogeneous [24]
[(aren)Cr(CO)3] Sorbic acid trans-Hex-2-enoic acid 40 Homogeneous [25]
[RuCl2{P(CH2)3OH}]2 Sorbic acid trans-Hex-4-enoic acid 82 Two-phase [26]
[RuCl2{P(CH2)3OH}]2 Sorbic acid cis-Hex-3-enoic acid 62 Homogeneous [26]
[Cp*RuCl(CO){P((CH2)3O Sorbic acid cis-Hex-3-enoic acid 66 Two-phase [26]
H)3}]
[Cp*Ru(MeCN)3]Tf Sorbic acid cis-Hex-3-enoic acid 67 Two-phase [27]
[Cp*Ru(MeCN)3]Tf Sorbic alcohol cis-Hex-3-en-1-ol 82 Two-phase [27]
[Cp*Ru(MeCN)3]Tf Ethylsorbate Ethyl-cis-hex-3-enoate 84 Two-phase [27]
[Cp*Ru(sorbic acid)]Tf Sorbic acid cis-Hex-3-enoic acid 96 Two-phase [28],
[31],
[32]
[Cp*Ru(sorbic alcohol)]Tf Sorbic alcohol cis-Hex-3-en-1-ol 94 Two-phase [28],
[31],
[32]
[Cp*Ru(sorbic aldehyde)]Tf Sorbic aldehyde No selectivity [38]
[Cp*Ru(methylsorbate)]Tf Methylsorbate Methyl-cis-hex-3-enoate 96 Two-phase and [38]
heteroegeneous
[Cp*Ru(butylsorbate)]Tf Butylsorbate Butyl-cis-hex-3-enoate 99 Two-phase and [38]
heterogeneous
[Cp*Ru(sorbic acid)]Tf Sorbic acid cis-Hex-3-enoic acid 97 Heterogeneous – [39]
hydrogen binding
[Cp*Ru(sorbic acid)]Tf Sorbic acid cis-Hex-3-enoic acid 97 Heterogeneous – [40]
ionic exchange
[Cp*Ru(sorbic alcohol)]Tf Sorbic alcohol cis-Hex-3-en-1-ol 85 Heterogeneous [39]
[RUCP*] FRAGMENT
The pentamethylcyclopentadienyl ligand (Cp*-ligand) is of particular importance in
organoruthenium chemistry due to its ability to stabilise unsaturated ruthenium complexes.
This property distinguishes it from the unsubstituted cyclopentadienyl ligand and is a result of
the higher electron density of the Cp*-ligand. The coordinately unsaturated particles are the
components of the catalytic cycle in the reactions catalyzed by transition metals.
The first work dealing with catalytic hydrogenation of sorbic acid using RuCp*
complexes were performed by Heinen [26],[27]. This author studied the
[Cp*Ru(CO)(PR3)Cl] and [Cp*Ru(CO)(PR3)]Tf (R = alkyl) complexes but they had low

catalytic activity. The [Cp*Ru(MeCN)3]Tf complex had significantly higher activity and
contained relatively simply substitutable acetonitrile ligands. The catalytically active particle
was probably the solvent stabilized lewis acid [RuCp*]+ fragment.
The usual entry to RuCp* chemistry begins from the dark brown dimeric (polymeric)
Ru(III) complex [Cp*RuCl2]2 that was examined independently in the groups of Bercaw [41]
and Suzuki[42] (equation 1).
2 RuCl3.3H2O + Cp*H [Cp*RuCl2]2 + 2 HCl + 3 H2O equation 1
This complex can be reduced [43] byLi[Et3BH] to [Cp*RuCl]4 and in accordance with
Koelle[44] using methanol in the presence of base to [Cp*Ru(μ-OMe)]2 (figure 6).
Cp*
Cp*
Cl Ru
Ru Cl
2 [Cp*RuCl2]2 + 4 Li[Et3BH] + 4 LiCl + BEt3
Ru Cl
Cp*
Cl Ru
Cp*
Me
O
[Cp*RuCl2]2 +3 MeOH + 2 K2CO3
Ru Ru
O
Me
Figure 6. Reduction[43] of [Cp*RuCl2]2.
Typical reactions [45] of the tetrameric [Cp*RuCl]4 complex are shown in Figure 7. Its
reaction with silver triflate in the presence of the well coordinating solvent acetonitrile gave
the [Cp*Ru(NCMe)3]Tf complex that was the necessary precursor for the [Cp*Ru(arene)]+
compounds. Ligands including CO, phosphines or dienes decomposed the tetramers, forming
18e- complexes such as [Cp*RuL2Cl]. Oxidative addition of allylchloride gave the 18e- -
Ru(IV)-complex [Cp*Ru(μ3-all)Cl2].
This complex offers the possibility of many different reactions that are shown in the
following scheme (figure 8). Detailed information is given in two reviews from Chaudret [46]
and Koelle [47]. Donor ligands such as dppm or bipy can be added [44] to the complex. The
methanolate bridges can be substituted by thiols [48] with retention of the structure. Treating
[Cp*Ru(μ-OMe)]2 with strong acid after methanol elimination gave the noncharacterized
solvent stabilized particle [Cp*Ru]+. This particle could be coordinated to by many different
ligands. [Cp*Ru]+ has a high affinity for 6π-electron systems as demonstrated by the
formation of [Cp*Ru(aren)]+ cations after the reaction with cyclic olefins and the elimination
of water. Through this the [Cp*Ru(C6H6)]Tf complex with two equivalents of hydrogen was
obtained [49] after the reaction of [Cp*Ru(μ-OMe)]2 with triflouromethanesulphonic acid and
cyclohexene at 80 °C in methylenechoride. Besides the activation of C-H bonds described,
the activation of C-C, C-O and C-Cl bonds could be also realized whereas C6-compounds
such as cyclohexene are aromatized.
CF3SO3-
Ru
MeCN NCMe
MeCN
+ AgTf, MeCN
+2L - AgCl
Cl
L = CO, PMe3
Ru 1/4 [Cp*RuCl]4 Ru
L Cl
Cl
+ dien + C6Me6 Cl
L
+NH4PF6
Ru Ru
Cl
Figure 7. Typical reactions[44] of [Cp*RuCl]4.
CONCLUSION
This text gave brief overview of the selective hydrogenation of sorbic acid and its
derivatives, especially sorbic alcohol, using organometallic complexes with different central
atoms to monounsaturated compounds. Trans-2 isomers can even be obtained using
heterogenous catalysts so the main goal was the preparation of the cis-3 isomers. The use of
different complexes based on Rh, Cr and Ru initially showed that the most selective
complexes were those based on Cr. But these are surpassed by complexes with the simple
structure [Cp*Ru(diene)]+ where the diene is the hydrogenated compound (sorbic acid or
sorbic alcohol or other derivative). The selectivities in these cases are up to 98 %. The
properties of these complexes are described in detail in the chapters.
OMe
Cp* Cp*
Ru Ru Ru OMe
OMe N N
PPh2 PPh2
C
H2
+dppm + 2,2´- bipyridin
[Cp*Ru(μ-OMe)]2
+RSH + CF3SO3H
Cp* Cp* +
SMe
Ru Ru
CF3SO3-
SMe Ru
+ (S)
+C6F6
80 °C
+ +
Tf -
Tf -
Ru Ru
F F
F F
F F
Figure 8. Typical reactions[47] of [Cp*Ru(OMe)]2.
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In: Homogeneous Catalysts: Types, Reactions and Applications ISBN: 978-1-61122-894-6
Chapter 12
HOMOGENEOUS CATALYZED SUCCINOYLATION

OF CELLULOSE IN IONIC LIQUIDS
C.F. Liu*1, A.P. Zhang1,2, W.Y. Li1, W. Lan1 and R.C. Sun1,3
1
State Key Laboratory of Pulp and Paper Engineering,
South China University of Technology, Guangzhou, China
2
Institute of of New Energy and New Material,
South China Agricultural University, Guangzhou, China
3
Institute of Biomass Chemistry and Technology,
Beijing Forestry University, Beijing, China
ABSTRACT
Homogeneous modification of sugarcane bagasse cellulose with succinic anhydride
(SA) was catalyzed with three different catalysts including iodine, N-bromosuccinimide
(NBS), and 4-dimethylaminopyridine (DMAP) in a solvent system containing 1-butyl-3-
methylimidazolium chloride ionic liquid ([C4mim]Cl) and dimethylsulfoxide (DMSO).
The effects of the mass ratio of catalyst/SA, reaction time, and reaction temperature on
the degree of substitute (DS) of cellulose were investigated. The results showed that the
DS of cellulosic derivatives increased to 0.56-1.54 under the experimental conditions
catalyzed with iodine, 0.92-2.31 with NBS, and 0.94-2.34 with DMAP, from 0.24
without any catalysts, indicating that these three catalysts were effective catalysts for
cellulose succinoylation in ionic liquids. The possible mechanism of homogeneous
succinoylation catalyzed with these catalysts and the actual role of these catalysts were
also investigated. Fourier transform infrared and solid-state cross-polarization/magic
angle spinning 13C NMR spectroscopies also provided evidence of catalyzed
homogeneous succinoylation reaction. The results indicated that the reaction of hydroxyl
groups at C-6, C-2, and C-3 positions in cellulose occurred.
Keywords: cellulose, succinoylation, catalyst, iodine, 4-dimethylaminopyridine, N-

bromosuccinimide, ionic liquids
* Corresponding author, chfliu@scut.edu.cn

388 C.F. Liu, A.P. Zhang, W.Y. Li et al.
1. INTRODUCTION
Recently, there is a growing urgency to develop novel bio-based products and other
innovative technologies that can unhook widespread dependence on fossil fuel around all over
the world [1]. Utilization of biomass, especially inedible lignocellulosic biomass, to create
biofuels, bioenergy, biochemicals, biocomposites and a host of other bioproducts has attracted
considerable attention around all over the world [2-4], even as one of the most important
policy-oriented research activities in developed countries. US Department of Energy has
targeted to achieve 10% of basic chemical building blocks arising from lignocellulose-derived
renewables by 2020, and a further increase to 50% by 2050 [1]. The European Union has also
developed a vision in which one-fourth of the EU’s transportation fuels will be derived from
biofuels by 2030 [5]. These political timetables result in critical challenges in biomass
utilization.
It has been estimated that about 50% of biomass in the world is lignocellulose, of which
polysaccharides including cellulose and hemicelluloses account for over two-thirds [6].
Chemically, cellulose is a homopolymer composed of D-glucopyranose units linked by β
(1→4) glycosidic bonds [7], much of which is in a crystalline structure. It is about 35-43% of
the dry lignocellulosic materials. Hemicelluloses, an amorphous complex polymer usually
composed of xylose, arabinose, galactose, glucose, and mannose, are the second most
abundant renewable materials after cellulose in plant cell walls [8], which account for about
25-35% of the dry lignocellulosic materials. The remainder is mostly lignin plus lesser
amounts minerals, waxes, and other compounds [9]. The utilization of these
biomacromolecules not only adds value to the biomass raw materials, but also contributes to
reduce environmental concerns regarding the disposal of the residues [10]. The integrated
utilization of lignocellulosic biomass is becoming the significant issue and development
tendency. In the promising utilization pattern, the lignocellulosic biomass is firstly
fractionated to three main components, that is, lignin, hemicelluloses, and cellulose, and then
the isolated components are independently utilized to produce different products according to
their own properties.
The promising applications of cellulose include biofibers, biopolymers, biofuels, and
biocomposites in native, degraded, or modified status [11,12]. Modification of cellulose
represents one of the most versatile transformations as it provides access to a variety of
biobased materials with valuable properties. Due to three hydroxyl groups available within
one anhydroglucose units (AGU) in cellulose, a great variety of chemical modifications of
cellulose are possible [13]. Chemical modifications of cellulose can introduce functional
groups into the macromolecules in heterogeneous phase or homogeneous phase to improve
the overall utilization of cellulosic polymers. Because more uniform and stable products can
be obtained in homogeneous phase than heterogeneous phase, homogeneous cellulose
functionalization has been one focus of cellulose research for a long time [14,15]. Acylation
of cellulose with linear chain acylation reagents such as anhydride or chloride is the most
common method to produce cellulosic bioproducts. Functionalization of cellulose using ionic
liquids (ILs), one of the most promising green solvents, as reaction media has attracted much
attention after cellulose was reported to be soluble in a variety of ILs with strong hydrogen
bond acceptors as anions, such as chloride [16-19], formate [20], acetate [21-23], and
alkylphosphate [20,24-26]. Cellulose acetylation with acetic anhydride or acetyl chloride has
Homogeneous Catalyzed Succinoylation of Cellulose in Ionic Liquids 389
been extensively studied because of the wide application of cellulose acetate, and the results
showed that cellulose acetates with high degree of substitution (DS) were easily prepared
[18,27-30]. Carbanilation with phenyl isocyanate [29,31], acylation with lauroyl chloride
[29], and perpropionylation with propionic anhydride [31] were also investigated in ILs. On
the other hand, modification of cellulose with cyclic anhydride such as succinic anhydride are
widely used to produce water absorbents for soil in agriculture, natural absorbents for the
removal of heavy metal ions in wastewater treatment, medicine for drug delivery systems,
and thermoplastic materials [32,33]. Moreover, the reaction results in a pendant carboxylic
moiety attached to the cellulose molecules via a covalent ester bond, providing a site upon
which further reactive chemistry is possible. However, our previous studies showed that
succinoylation was much more difficult than acetylation, and only the cellulose derivatives
with relatively low DS were obtained [34,35].
To increase cellulose succinoylation efficiency, three different catalysts including iodine
(I2), 4-dimethylaminopyridine (DMAP) and N-bromosuccinimide (NBS) were explored in a
reaction medium containing ionic liquid 1-butyl-3-methylimidazolium chloride ([C4mim]Cl)
based on their good catalytic effects on the esterification of alcohols. The cellulosic
derivatives were then characterized by Fourier transform infrared (FT-IR), and solid-state
CP/MAS 13C nuclear magnetic resonance (NMR) spectroscopies. The possible mechanisms
of catalyzed succinoylation were discussed.
2. EXPERIMENTAL
2.1. Materials
Sugarcane bagasse (SCB) was obtained from Guangzhou, China. It was dried in sunlight
and then cut into small pieces. The cut SCB was ground and screened to prepare 20-40 mesh
size particles (450-900 μm). Cellulose was isolated after delignification of ground SCB with
sodium chlorite at pH 3.8-4.0 followed by alkaline extraction with 10% potassium hydroxide.
Ionic liquid [C4mim]Cl was obtained from the Chemer Chemical Co., Ltd., Hangzhou,
China, and used as received. All of other chemicals used were of analytical grade and
purchased from Sigma-Aldrich, Guangzhou, China.
2.2. Homogeneous Succinoylation of Cellulose Catalyzed with

I2, NBS, and DMAP
Dried SCB cellulose was added to [C4mim]Cl in three-necked flask. The mixture of
cellulose/[C4mim]Cl was stirred up to 10 h at 80 oC under N2 atmosphere to guarantee the
complete dissolution of cellulose. To the resulting cellulose solution, 5 mL of DMSO was
added to reduce viscosity and achieve a suitable mixing. Then catalyzed succinoylation
reaction was carried out according to the following procedures.
2.2.1 Succinoylation Catalyzed with I2

I2 and SA was dissolved in 5 mL DMSO, and then added to the cellulose solution in
[C4mim]Cl/DMSO system at the corresponding reaction conditions shown in Table 1. The
mixture was stirred under N2 atmosphere for the desired time. After the required time, 2 mL
of saturated solution of sodium thiosulfate was added to the modified cellulose solution with
agitation. The mixture was vigorously shaken for 2 min to guarantee complete transformation
of iodine to iodide. Then the resulted mixture was slowly poured into 150 mL of isopropanol
with agitation. The residues were filtrated out, washed thoroughly with isopropanol to
eliminate ILs, unreacted anhydride, and byproducts, and then dried in a vacuum at 50 oC for
16 h.
2.2.2. Succinoylation Catalyzed with NBS

NBS and SA was dissolved in 5 mL DMSO, and then added to the cellulose solution in
mixture was stirred under N2 atmosphere for the desired time. After the required time, the
resulted mixture was slowly poured into 150 mL of isopropanol with agitation. The residues
were filtrated out, washed thoroughly with isopropanol to eliminate ILs, unreacted anhydride,
and byproducts, and then dried in a vacuum at 50 oC for 16 h.
2.2.3. Succinoylation Catalyzed with DMAP

DMAP and SA was dissolved in 5 mL DMSO, and then added to the cellulose solution in
mixture was stirred under N2 atmosphere for the desired time. After the required time, the
resulted mixture was slowly poured into 150 mL of isopropanol with agitation. The residues
were filtrated out, washed thoroughly with isopropanol to eliminate ILs, unreacted anhydride,
and byproducts, and then dried in a vacuum at 50 oC for 16 h.
2.3. Determination of Degree of Substitution
The DS of cellulosic derivatives was determined by direct titration method [36,37]. A

known weight of the sample was dissolved in 10 mL of DMSO by stirring at 75 oC for 30
min. After cooling, 5-6 drops of phenolphthalein indicator were added. This solution was
titrated against 0.01 M standard NaOH solution until a permanent pale pink color was seen.
The DS was calculated by using the following equation:
where 162 g/mol is the molar mass of an AGU, 100 g/mol is the net increase in the mass of an
AGU for each succinoyl substituted, m is the weight of sample analyzed, VNaOH is the volume
of standard NaOH solution consumed in the titration, and cNaOH is the molarity of standard
NaOH solution.
2.4. Characterization of the Native and Succinylated Cellulose
Viscosity of the cellulose was measured by British Standard Methods for determination
of limiting viscosity number of cellulose in dilute solutions, Part 1, cupriethylenediamine
(CED) method (BS 6306, Part 1, 1982). The viscosity average DP (degree of polymerization)
of cellulose was estimated from their intrinsic viscosity [η] in CED hydroxide solution,
P0.90=1.65[η], where P is an indeterminate average DP [38]. Molecular weight (Mw) of
cellulose was then calculated from P by multiplied by 162, the Mw of an AGU.
The FT-IR spectra of the cellulose and succinylated cellulosic derivatives were recorded
on an FT-IR spectrophotometer (Nicolet 510) from finely ground samples (1%) in KBr pellets
in the range 4000-400 cm-1. Thirty-two scans were taken for each sample with a resolution of
2 cm-1 in the transmission mode.
The solid-state CP/MAS 13C NMR spectra were obtained on a Bruker DRX-400
spectrometer with 5 mm MAS BBO probe employing both Cross Polarization and Magic
Angle Spinning and each experiment was recorded at ambient temperature. The spectrometer
operated at 100 MHz. Acquisition time was 0.034 s, the delay time 2 s, and the proton 90o
pulse time 4.85 μs. Each spectrum was obtained with an accumulation of 5000 scans.
3. RESULTS AND DISCUSSION

3.1. Succinoylation Catalyzed with Iodine
Delignification of SCB with sodium chlorite followed by alkaline extraction yielded

49.6% cellulose (based on the dry weight of SCB). The intrinsic viscosity, degree of
polymerization, and molecular weight of the isolated cellulose were determined to be 378
mL·g−1, 1277, and 206800 g·mol−1, respectively.
Figure 1. Scheme for succinoylation of SCB cellulose with succinic anhydride.
Usually, SA reacts with cellulose O-H groups to form the monoester as shown in Figure
1. In the present study, succinoylation of the obtained cellulose with different catalysts in
[C4mim]Cl/DMSO system was investigated to improve cellulose derivatizing efficiency.
After cellulose was dissolved in [C4mim]Cl, the viscous cellulose solution obtained was
diluted by DMSO to achieve suitable and clear mixture. Solid acylation reagent SA and
catalysts previously dissolved in DMSO were added to the diluted solution to achieve
homogeneous succinoylation reaction. Iodine has been reported recently as an effective
catalyst for acetylation of alcohols and polysaccharides without solvents [39,40]. In the
present study, we investigated the possibility of cellulose succinoylation catalyzed with iodine
in [C4mim]Cl/DMSO to increase cellulose modification efficiency. Table 1 shows the effects
of the parameters, including the mass ratio of I2/SA from 2% to 15%, reaction temperature
from 85 to 110 oC, and reaction duration from 30 to 120 min, on DS of the succinylated
cellulose.
As shown in Table 1, compared with that obtained under the same conditions without any
catalysts (DS=0.24, data not shown), DS of cellulose derivative obtained with the addition of
2% iodine (based on SA) increased to 0.56. This increment indicated that the efficiency of
succinoylation in the presence of iodine increased, suggesting that iodine could be an
effective catalyst for cellulose succinoylation in ionic liquids. The improvement of iodine
dosage from 2% to 5%, 8%, 10% and 15% (based on SA) resulted in an improvement of the
DS of cellulose derivatives from 0.56 to 0.84, 1.28, 1.41 and 1.39, respectively. Prolonging
reaction duration from 30 min to 45, 60, and 90 min led to an increment in DS from 0.72 to
0.97, 1.41 and 1.52 respectively. However, DS decreased from 1.52 to 1.34 with a further
increment of reaction duration from 90 min to 120 min. This decrement was probably due to
the further reaction of succinic acid attached to cellulose with hydroxyl group in the near
surroundings to form diesters in the presence of iodine. Raising reaction temperature from 85
o
C to 90, 95, 100, 105 and 110 oC resulted in an increase in DS from 0.64 to 0.78, 0.92,
1.41,1.46 and 1.54, respectively. However, the maximum DS observed was only about half of
the theoretical maximum vale 3. The similar decreased acylation of cellulose modified with
lauroyl chloride was also reported in ILs [29].
Table 1. DS of succinylated cellulose with succinic anhydride in [C4mim]Cl/DMSO using

iodine as a catalyst.
Succinoylation conditions Succinylated cellulose

Cellulose (%) Molar ratioa I2/SA (%) Temperature (oC) Duration (min) Sample No. DS
2.0 4:1 2 100 60 1 0.56
2.0 4:1 5 100 60 2 0.84
2.0 4:1 8 100 60 3 1.28
2.0 4:1 10 100 60 4 1.41
2.0 4:1 15 100 60 5 1.39
2.0 4:1 10 100 30 6 0.72
2.0 4:1 10 100 45 7 0.97
2.0 4:1 10 100 90 8 1.52
2.0 4:1 10 100 120 9 1.34
2.0 4:1 10 85 60 10 0.64
2.0 4:1 10 90 60 11 0.78
2.0 4:1 10 95 60 12 0.92
2.0 4:1 10 105 60 13 1.46
2.0 4:1 10 110 60 14 1.54
a
Molar ratio of SA to anhydroglucose unit (SA/AGU) in cellulose was 4:1.
In present study, the DS of cellulose derivatives increased from 0.24 without any
catalysts to the range of 0.56-1.54 in the presence of iodine catalyst under the conditions
given. The possible mechanism of iodine-catalyzed succinoylation and the actual role of
iodine are not clear. However, a plausible explanation is that iodine might first be ionized into
I+ and I− in ILs. I+ in turn activates the carbonyl groups of SA to form as the acylation reagent
for further reaction, as shown in Figure 2.
Figure 2. Possible mechanism of the iodine-catalyzed succinoylation of cellulose.
3.2. Succinoylation Catalyzed with NBS
NBS is an inexpensive and commercially available reagent that is traditionally used as an

oxidizing agent or brominating agent in radical reactions and various electrophilic additions
[41]. It is also a mild and efficient catalyst for acetylation of alcohols and phenols under mild
reaction conditions [42]. In present study, cellulose succinoylation was discussed in
[C4mim]Cl/DMSO system using 4:1 molar ratio of SA/AGU in cellulose, a mass ratio of
NBS/SA between 0 and 20%, reaction temperature 90-120oC and reaction duration 30-240
min.
Table 2 shows the DS of cellulose derivatives obtained with NBS catalyst. The addition
of 1% NBS (based on SA) resulted in the DS enhancement from 0.24 to 1.27, indicating the
significant improvement of succinoylation in the presence of NBS. An increase of NBS/SA
mass ratio from 1% to 2% and 5% resulted in noticeable improvement of DS from 1.27 to
1.84 and 2.31, respectively. Clearly, the efficiency of cellulose succinoylation in
[C4mim]Cl/DMSO system was significantly enhanced with catalysis of NBS compared with
that without any catalysts. However, further improvement of NBS/SA mass ratio from 5% to
10% and 20% led to a reduction of DS from 2.31 to 1.55 and 1.23, respectively. The reason of
this decrease in DS was probably due to the formation of diester in the presence of catalyst
NBS by crosslinking of the produced succinic acid attached to cellulose, i.e., monoester, with
other free hydroxyl groups in the surroundings. This decrement was also found in iodine-
catalyzed succinylation. These results indicated that NBS could significantly improve the
reaction efficiency of SA and cellulose in [C4mim]Cl/DMSO system. DS of cellulose
derivatives reached 0.92 within 30 min, 1.31 with 45 min, 1.84 within 60 min, 1.92 in 75 min,
1.99 in 90 min, and 2.03 in 120 min when keeping the molar ratio of SA/AGU at 4:1, reaction
temperature at 100 oC and NBS/SA mass ratio at 2%. Higher reaction temperature was also
favorable to NBS-catalyzed succinoylation. Improving reaction temperature from 90 to 95,

100, 110 and 120 oC resulted in an enhancement in DS of cellulose derivatives from 1.67 to
1.74, 1.84, 1.98 and 2.25, respectively.

NBS as a catalyst.
Succinoylation conditions Succinylated cellulose

Cellulose (%) Molar ratioa NBS/SA (%) Temperature (oC) Duration (min) Sample No. DS
2.0 4:1 1 100 60 15 1.27
2.0 4:1 2 100 60 16 1.84
2.0 4:1 5 100 60 17 2.31
2.0 4:1 10 100 60 18 1.55
2.0 4:1 20 100 60 19 1.23
2.0 4:1 2 100 30 20 0.92
2.0 4:1 2 100 45 21 1.31
2.0 4:1 2 100 75 22 1.92
2.0 4:1 2 100 90 23 1.99
2.0 4:1 2 100 120 24 2.03
2.0 4:1 2 100 240 25 1.73
2.0 4:1 2 90 60 26 1.67
2.0 4:1 2 95 60 27 1.74
2.0 4:1 2 110 60 28 1.98
2.0 4:1 2 120 60 29 2.25
a
Figure 3. Possible mechanism of the NBS-catalyzed succinoylation of cellulose.

The DS of cellulose derivatives increased from 0.24 without any catalysts to the range of
0.92-2.31 in the presence of NBS catalyst under the conditions given. The possible
mechanism of NBS-catalyzed succinoylation is shown in Figure 3. NBS might act as a source
for Br+, which in turn activates the carbonyl groups of SA to produce the highly reactive
acylating agent. This acylating agent reacts with hydroxyl groups of cellulose, which produce
succinoylated cellulose upon elimination of NBS.
3.3. Succinoylation Catalyzed with DMAP
Pyridine has been found to be effective in the modification of wood with various long
chain anhydrides, because it serves not only to swell the wood structure, thereby permiting
effective ingress of reagent, but also catalyzes the reaction via nucleophilic mediated catalysis
[43]. DMAP is a derivative of pyridine with the chemical formula (CH3)2NC5H4N. It is a very
useful nucleophilic catalyst for a variety of reactions such as esterifications of alcohols with
anhydrides. In comparison to pyridine, DMAP was found to be approximately 104 times more
active when used as acylation catalyst [44]. It has been used in the synthesis of
agrochemicals, pharmaceuticals and polymers as an acylation catalyst. In present study, we
investigated the possibility of succinoylation catalyzed with DMAP in ILs. Table 3 shows the
effects of the mass ratio of DMAP/SA from 1% to 15%, reaction temperature from 60 to 110
o
C, and reaction duration from 30 to 120 min on DS of cellulose derivatives succinylated in
[C4mim]Cl/DMSO system.

DMAP as a catalyst.
Succinoylation conditions Succinylated

cellulose
Cellulose (%) Molar ratioa DMAP/SA (%) Temperature Duration (min) Sample No. DS
(oC)
2.0 4:1 1 80 60 30 0.94
2.0 4:1 2 80 60 31 1.19
2.0 4:1 3 100 60 32 1.52
2.0 4:1 5 80 60 33 1.78
2.0 4:1 8 80 60 34 1.88
2.0 4:1 15 80 60 35 1.69
2.0 4:1 5 60 60 36 1.55
2.0 4:1 5 70 60 37 1.75
2.0 4:1 5 90 60 38 2.19
2.0 4:1 5 100 60 39 2.34
2.0 4:1 5 110 60 40 1.93
2.0 4:1 5 80 30 41 1.28
2.0 4:1 5 80 45 42 1.52
2.0 4:1 5 80 90 43 1.49
2.0 4:1 5 80 120 44 1.38
a
As shown in Table 3, DS of cellulose derivative increased to 0.94 with addition of 1%

DMAP (based on SA), indicating the enhanced succinoylation efficiency in
[C4mim]Cl/DMSO in the presence of DMAP. The DS was improved from 0.94 to 1.19, 1.52,
1.78, and 1.88 with the enhancement of DMAP/SA mass ratio from 1% to 2%, 3%, 5%, and
8%, respectively. Further improvement of DMAP dosage from 8% to 15% led to slight
decrease in DS from 1.88 to 1.69. The increase of reaction temperature from 60 to 70, 80, 90
and 100 oC resulted in an improvement of DS from 1.55 to 1.75, 1.78, 2.19, and 2.34,
respectively. DS was slightly reduced from 2.34 to 1.93 with further improvement of reaction
temperature from 100 to 110 oC. Holding DMAP/SA mass ratio at 5%, reaction temperature
at 80 oC and molar ratio of SA/AGU at 4:1, DS of cellulose derivatives reached 1.28 within
30 min, 1.52 in 45 min, and 1.78 in 60 min. However, DS decreased from 1.78 to 1.49 and
1.38 with further elongation of reaction duration from 60 min to 90 and 120 min, respectively.
The DS of cellulose derivatives increased to the range of 0.94-2.34 in the presence of
DMAP catalyst under the conditions given. The possible mechanism of DMAP-catalyzed
succinoylation of cellulose is similar to DMAP-catalyzed acetylation. Figure 4 illustrated the
possible role of DMAP in catalyzed succinoylation. The nucleophilic attack of DMAP on a
carbonyl group of succinic anhydride leads to intermediate, which could react with cellulose
hydroxyl groups and produce cellulose ester.
Figure 4. Possible mechanism of the DMAP-catalyzed succinoylation of cellulose.
3.4. FT-IR Spectra
Figure 5 illustrates the FT-IR spectra of native cellulose and succinylated cellulose with
or without catalysts. In spectrum 1, the absorbances at 3434, 2929, 1633, 1372, 1164, and
1049 cm-1 are associated with native cellulose. The strong adsorption at 3434 cm-1 is
attributed to the stretching of hydroxyl groups and that one at 2929 cm-1 corresponds to the C-
H stretching. The band at 1633 cm-1 relates to the bending mode of the absorbed water. The
peak at 1372 cm-1 is due to the O-H bending. The absorption band at 1164 cm-1 corresponds
to C-O antisymmetric bridge stretching [45]. A strong peak at 1049 cm-1 arises from C-O-C
pyranose ring skeletal vibration [46].
Compared with spectrum 1, spectrum 2 of succinylated cellulose without any catalyst

provides evidence of succinoylation by the occurrence of the absorbance at 1728 and 1574
cm-1. The former band at 1728 cm-1 is an overlapping of the absorptions by carbonyl groups
in carboxyl acids and esters [47]. The latter band at 1574 cm-1 is originated from
antisymmetric stretching of carboxylic anions [33], indicating the formation of monoester.
More importantly, spectrum 3 of succinylated cellulose with iodine catalyst provides the more
evidences of catalyzed succinoylation. The intensities of the two peaks at 1728 cm-1 for
carbonyl groups and at 1574 cm-1 for carboxylic anions significantly increased. In addition,
the intensity of the absorption band at 1164 cm-1 for C-O antisymmetric stretching clearly
increased after succinoylation, suggesting that the catalyzed esterification reaction does occur.
100 1
95
2
90
85
80
75 1633
3
70
%T
1372
65
60
55 1574
2929
50 1412
45
1049
1164
40 3434 1728
3500 3000 2500 2000 1500 1000

Wavenumbers (cm-1)
Figure 5. FT-IR spectra of unmodified cellulose (spectrum 1), succinylated cellulose without any
catalyst (spectrum 2) and with iodine as a catalyst (spectrum 3, sample 7).
Similar results were also found in the FT-IR spectra of succinylated cellulose samples
catalyzed with NBS and DMAP (spectra not shown). It indicated that iodine, NBS and
DMAP are efficient catalysts of cellulose succinoylation in [C4mim]Cl/DMSO. As expected,
the absence of peaks at 1850 and 1780 cm-1 in spectra 2 and 3 for succinylated cellulose
confirmed that the products are free of the unreacted SA.
3.5. Solid-State CP/MAS 13C-NMR
In the present study, the catalyzed succinoylation reaction of cellulose was also studied
by solid-state CP/MAS 13C-NMR spectroscopy, and the spectra of unmodified cellulose
(spectrum a), succinylated cellulose without any catalysts (spectrum b) and with NBS as a
catalyst (spectrum c, sample 13) are shown in Figure 6.
PPM
Figure 6. Solid state CP/MAS 13C-NMR spectra of unmodified cellulose (spectrum a), succinylated
cellulose without any catalysts (spectrum b) and with NBS as a catalyst (spectrum c, sample 15).
As shown in Figure 6, all noticeable signals in spectrum a of unmodified cellulose are

distributed in the region between 50 and 110 ppm for the carbon atoms of the carbohydrate
moiety. Clearly, the signals at 85.2 ppm for C-4 of crystalline cellulose and 61.1 ppm for C-6
of crystalline cellulose disappeared in spectra b and c of succinylated cellulose, suggesting the
complete disruption of cellulose crystalline structure during the dissolution and
functionalization, which indicated that succinoylation reaction occurs in homogeneous phase.
Evidently, the presence of the signals at 171.0 ppm for carboxylic group and 26.4 ppm for
methylene group also provided evidence of succinoylation, which indicated the reaction
shown in Figure 1 does occur. In spectrum c of cellulose derivative succinylated with NBS
catalyst, the intensities of the signals at 171 ppm for carboxylic group and 26.4 ppm for
methylene group significantly increased compared with that in spectrum b without any
catalysts, indicating that NBS could significantly improve the modification efficiency of
cellulose with SA in [C4mim]Cl/DMSO system. The three free hydroxyl groups at C-6, C-2,
and C-3 position in AGU are the main reactive sites in cellulose. As shown in Figure 6, the
intensity of the signal for C-6 decreased after succinoylation, and that at 67.8 ppm for C-2 and
C-3 also decreased, which indicated the succinoylation reaction at C-6, C-2, and C-3 positions
does occur. The similar observations were also found in the spectra of cellulose derivatives
catalyzed with iodine and DMAP (spectra not shown). These results suggested that iodine,
NBS, and DMAP are effective succinoylation catalysts of cellulose in [C4mim]Cl/DMSO.
CONCLUSION
The homogeneous modification of sugarcane bagasse cellulose with succinic anhydride
in solvent system containing ionic liquid 1-butyl-3-methylimizolium chloride and
dimethylsulfoxide was catalyzed with three different catalysts including iodine, NBS, and
DMAP. The results showed that these three catalysts could effectively improve the cellulose
succinoylation. Under the given conditions the DS of cellulose derivatives increased from
0.24 to 0.56-1.54 with iodine catalyst, 0.92-2.31 with NBS catalyst, and 0.94-2.34 with
DMAP catalyst. The possible mechanisms of homogeneous catalyzed succinoylation were
also proposed. FT-IR and solid-state CP/MAS 13C-NMR spectroscopies also provided
evidence for catalyzed succinoylation. The results indicated that the reaction of hydroxyl
groups at C-6, C-2, and C-3 positions in cellulose all occurred.
ACKNOWLEDGMENTS
The authors are grateful for the financial support of this research from the National
Natural Science Foundation of China (Nos. 30871994, 30972325, and 30710103906), the
Guangdong Natural Science Foundation (No. 8451064101000409), Specialized Research
Fund for the Doctoral Program of Higher Education (No. 20070561040), Chinese
Universities Scientific Fund (No. 2009ZZ0024), and National Basic Research Program of
China (No. 2010CB732201)
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Chapter 13
PALLADIUM COMPLEXES OF N-HETEROCYCLIC

CARBENES IN HOMOGENEOUS CATALYSIS
AND BIOMEDICAL APPLICATIONS *
Chandrakanta Dash and Prasenjit Ghosh*

Department of Chemistry
Indian Institute of Technology Bombay,
Powai, Mumbai 400 076, India
ABSTRACT
The knowledge of the efficient formation of C−X (X = C and N) bonds
asymmetrically or otherwise is vital to contemporary organic synthesis. In this context
notable is the contribution of Pd towards the development of the area. The specialty of Pd
as a metal lies in its ability to efficiently construct numerous types of C−X (X = C, N, O
and S) bonds under ambient conditions. A key strength of Pd mediated synthesis thus lies
in its chemo- and regio selectivities that facilitate the synthesis of intricate target
molecules otherwise not conveniently accessible by traditional methods. Furthermore, Pd,
being a late transition metal, inherently possesses important attributes like, the air and
moisture stability and the functional group tolerance, which often are the key ingredients
of a successful catalyst. Of late, the N-heterocyclic carbenes (NHC) have added a new
chapter in the design, discovery and development of Pd catalysts, thereby generating an
enormous interest in its palladium complexes in recent years. The strong σ-donating
nature of the N-heterocyclic carbene ligand in the catalyst allows oxidative insertions of
challenging substrates while the ligand topological steric demands promote the fast
reductive elimination reactions, which together constitute two important steps in
numerous catalysis cycles. Additionally, the strong palladium−N-heterocyclic carbene
(Pd−NHC) interaction help stabilizes many catalytically important active species at low
*
A version of this chapter was also published in Palladium: Compounds, Production and Applications , edited by
Kenneth M. Brady, Nova Science Publishers. It was submitted for appropriate modifications in an effort to
encourage wider dissemination of research.
*
Email: pghosh@chem.iitb.ac.in, Fax: +91-22-2572-3480.
404 Chandrakanta Dash and Prasenjit Ghosh
ligand to Pd ratios and also at high temperatures thereby broadening its scope of catalytic
applicability. Apart from the C−X (X = C and N) bond forming reactions, the Pd
complexes of N-heterocyclic carbenes perform various other reactions like the oxidation
reactions, Tsuji-Trost reaction and the polymerization reactions etc. Even extending
further beyond chemical catalysis, the palladium N-heterocyclic carbene complexes
exhibit promising potential in various biomedical applications like in the anticancer
studies.
INTRODUCTION
Smart and efficient formation of strategic bonds represents a perennial challenge in the
world of organic synthesis and has largely propelled the development of various types of C−X
(X = C, N, O and S) bond forming reactions into powerful synthetic tools in the ever
expanding arsenal of organic methodologies.[1] In this context the transition metals occupy a
special place particularly for their role in both the stochiometric and catalytic bond
formations[2].Notable is the versatility of palladium that makes it interesting among metals
for the expedient construction of numerous C−X bonds (X = C, N, O and S) in varied
challenging environments and thereby thriving as a metal of choice under catalytically
demanding situations.[3,4] The metal’s popularity stems from providing convenient access to
key steps of various preparative protocols for the compounds of industrial and academic
interests.[5] The other important attributes of palladium lie in its robustness and high air and
moisture stabilities that facilitate indefinite storage and easy handling of its compounds.
Additionally, the palladium catalysts are often functional group tolerant thus allowing it to
function in synthetically delicate conditions. Though numerous catalysis with palladium have
long been reported under the “Ligand Assisted Catalysis” (LAC) conditions,[6] the use of
well-defined catalysts is advantageous in many respects like in maintaining a strict control of
the optimal 1:1 palladium/ligand ratio, that avoid not only the large use of expensive ligands
but also eliminate the excess ligand removal step at the end of the catalysis.
The N-heterocyclic carbenes (NHCs) are fast emerging as an important ancillary ligand
of choice that provide an appropriate platform for designing effective transition metal
catalysts for a variety of important transformations in recent years. They are often seen as
convenient alternatives to the phosphines, N- and O-donor ligands ubiquitous in numerous
homogeneous catalysts.[7,8] The N-heterocyclic carbenes are good σ-donors[9] that favor
strong binding to metals in general, and thereby prevent catalyst leaching, an important
attribute of a successful catalyst, owing to reduced ligand dissociation. Furthermore, because
of their tighter binding, the N-heterocyclic carbenes stabilize many catalytically relevant
intermediates via a combination of electronic and steric effects. Thus, the rising status of the
N-heterocyclic carbene catalysts can be attributed to their superior performance, ease of
preparation, air and moisture stability, non-toxicity and the high efficiency at low catalyst
loading. A prominent hallmark of the palladium complexes in general and its N-heterocyclic
carbene ones in particular is their ability to efficiently execute the catalytic formation of a
variety of C−X (X = C and N) bonds under amenable conditions, which is in sharp contrast to
the other frequently encountered alkali and transition metal based reagents like that of Li, Mg
and Zn etc. that mostly participate in stoichiometric bond formations and also, being
extremely air and moisture sensitive, require stringent handling measures.
Palladium Complexes of N-Heterocyclic Carbenes … 405
Remarkable is the ever growing portfolio of catalytic transformations partaken by

palladium N-heterocyclic carbene complexes that span from the C−C bond forming reactions
namely, the Suzuki–Miyaura, Heck–Mizoroki, Sonogashira, Hiyama, Kumada-Tamao-Corriu,
Negishi, Stille, α-ketone arylation, hydroarylation and carbonylation reactions to the C−N
bond formations like the aryl amination and hydroamination reactions. The monograph
presents recent developments in the emerging utility of palladium N-heterocyclic carbene
complexes in the homogeneous catalysis and in their newly evolving biomedical applications.
The flexibility in conveniently shuttling between different oxidation states allows palladium
to participate in numerous catalytic cycles involving oxidation and reduction sequences in the
form of oxidative addition and reductive elimination steps. Though Pd(0)/Pd(II) shuttle is
more commonly encountered, the Pd(II)/Pd(IV) shuttle too have been reported in some cases.
b
In this context the well-characterized examples of the Pd(0), Pd(II) and Pd(IV) complexes of
N-heterocyclic carbenes assume relevance. Additionally, the electronic effects of palladium,
being a second row transition element, provide optimal reactivity for catalysis as the first row
ones are noted for their high reactivity while the third row ones are comparatively inert and
hence the both of these are not so effective as catalysts compared to the second row metals on
many occasions.
Palladium(0) N-Heterocyclic Carbene Complexes
Recognizing the importance of Pd(0)/Pd(II) shuttle in many catalytic cycles, there have
been conscious efforts in the past toward directly accessing these catalytic cycles through
well-characterized intermediates. In this regard several Pd(0) complexes (1−21) of N-
heterocyclic carbenes[10] have been synthesized (Figure 1), some even structurally
characterized, and subsequently employed in various catalysis like the, Suzuki−Miyaura,
b,c,e,f,h
Heck–Mizoroki, e,i Sonogashira, g telomerization of 1,3-dienesd and aryl aminationb,g
reactions etc. Though much rare compared to the Pd(II) counterparts, the Pd(0) N-
heterocyclic carbene complexes have been synthesized primarily by employing two
successful strategies. First one, the simplest of the two approaches, involved the direct
reaction of a Pd(0) species with a N-heterocyclic carbene ligandd,e,h,i,j (Scheme 1), while the
second method involved either the reduction of a Pd(II) species in presence of a N-
heterocyclic carbene ligand or the direct reduction of a palladium(II) N-heterocyclic carbene
complex itself (Scheme 2) to yield the desired palladium(0) N-heterocyclic carbene complex.
a,b,c,f,g
Palladium(II) N-Heterocyclic Carbene Complexes
Among the three oxidation states, the Pd(II) is by far the most commonly observed one
with the contemporary literature inundated with numerous palladium(II) N-heterocyclic
carbene complexes mainly because of their new-found success in homogeneous catalysis. The
palladium(II) N-heterocyclic carbene complexes are primarily synthesized by any of the
following three routes, (i) by transmetallation of the silver N-heterocyclic carbene complexes,
obtained from the reaction of an azolium salt and Ag2O, with Pd(II) precursors,[11] (ii) by the
direct reaction of the azolium salts with Pd(II) precursors in presence of a base[12] and (iii)
lastly, by the oxidative addition of an activated C−H bond in an azolium salt on the metal
center of a Pd(0) precursor (Scheme 3).[13]
Figure 1.
(NHC)2Pd (NHC)2Pd
Pd(0) (PR3)2Pd
NHC
Pd(0) (COD)Pd(alkene)
(alkene)
(NHC)Pd(alkene) (NHC)2Pd(alkene)
Scheme 1.
reduction
[Pd(allyl)Cl]2 (NHC)2Pd
NHC
reduction
(NHC)Pd(allyl)Cl (NHC)Pd(L)
L (L = PR3 or NHC)
Scheme 2.
Scheme 3.
Palladium(IV) N-Heterocyclic Carbene Complexes
The Pd(IV) species are extremely rare compared to the Pd(0) and Pd(II) species and
consequently, the Pd(II)/Pd(IV) shuttle is less invoked than the Pd(0)/Pd(II) shuttle in various
palladium mediated catalytic cycles. The structurally characterized example of a Pd(IV) N-
heterocyclic carbene complex (22) (Figure 2) remained elusive until recently with the
appearance of a report of a Pd(IV) N-heterocyclic carbene complex synthesized judiciously
by the oxidative addition of two chloride ligands to a Pd(II) complex, Pd[OCMe2CH2(1-
C{NCHCHNiPr}][benzo(h)quinoline], using PhICl2 (Scheme 4).[14]
Figure 2.
Scheme 4.
The monograph next discusses the various catalysis performed by palladium N-

heterocyclic carbene complexes.
C−C Bond Forming Reactions
Palladium mediated catalytic C−C bond formations under amenable conditions have
revolutionized the world of organic synthesis in the last few decades and have emerged as
versatile synthetic tools for the smart and expedient preparations of numerous target
molecules today. Though the phosphines have traditionally enjoyed a wide spread utility in
palladium mediated catalysis, of late, the N-heterocyclic carbenes are seeing unprecedented
popularity in this area, even surpassing the phosphines on many occasions.
Suzuki–Miyaura Cross-Coupling Reaction
The Suzuki–Miyaura reaction, involving the palladium catalyzed C−C cross-coupling of

organoboron derivatives with aryl-, vinyl- or alkyl halides, is among the highly used methods
available today for the construction of the biaryl frameworks ubiquitous in numerous
bioactive molecules, pharmaceuticals and natural products (Scheme 5). The popularity of the
reaction primarily arises from its tolerance towards a broad range of functional groups and
from the several other advantages normally associated with the use of organoboron reagents
like its ease of accessibility, convenience in product isolation and minimal toxicity issues.
The N-heterocyclic carbenes have largely propelled the development of the Suzuki–
Miyaura C–C cross-coupling reaction in the last two decades to an extent that the reaction is
now finding routine use in both industry and academia alike. It is worth mentioning that the
N-heterocyclic carbenes were originally introduced by Hermann as late as in 1998[15] in the
Suzuki–Miyaura reaction long after the initial discovery of the cross-coupling reaction by
Suzuki and Miyaura in 1979.[16] Initial phases of the developments of the catalyst design and
discovery for the coupling reaction mainly rode on the back of phosphine based systems till
the advent of N-heterocyclic carbenes in this area.
Particularly interesting is the Suzuki–Miyaura cross-coupling of aryl chloride substrates,
which are more challenging by virtue of being less reactive in contrast to the aryl iodide and
bromide ones that readily undergo the cross-coupling reaction. The aryl chlorides, being more
abundant, diverse and inexpensive, are in great demand for use as substrates for the cross-
coupling reaction. Thus, though obvious, a formidable challenge, from both the academic and
industrial perspectives, lies in utilizing the cheap and readily available aryl chlorides for the
cross-coupling reaction. The difficulty of achieving the Suzuki–Miyaura coupling of aryl
chlorides largely stems from the stronger C−Cl bond than the other C–X (X = Br, I) bonds
[bond dissociation energy (kcal/mol) for Ph–X: Cl (95), Br (80) and I (65)],[17] thereby
making the coupling of aryl chlorides a topic of contemporary interest. In this regard it is
worth mentioning that significant efforts have been made toward developing catalysts for the
coupling of aryl chlorides with the first breakthrough appearing only in 1998 using custom-
built sterically demanding phosphine systems,[18] nearly two decades after the initial
discovery of the Suzuki–Miyaura reaction with the aryl bromide substrates,[16] and thereby
underscoring the underlying challenges associated with the coupling of aryl chlorides.
In keeping with the phenomenal successes of N-heterocyclic carbenes in catalysis,
numerous attempts have been made in recent years in exploring their potential in the
Suzuki−Miyaura cross-coupling reaction.[19] Specific emphasis lay on designing suitable
catalysts exhibiting high turnover numbers (TONs) or the ones with the ability to perform
more challenging and also synthetically coveted aryl chloride coupling.
The catalysis studies were performed either under “Ligand Assisted Catalysis” (LAC)
conditions, involving the in situ generation of an active catalyst from the ligand and a metal
precursor, or using well-defined precatalysts. Among the “Ligand Assisted Catalysis” (LAC)
reported with the N-heterocyclic carbenes, notable is an unsymmetrically substituted
imidazolium bromide salt 31 (Figure 3) which in presence of a palladium(0) precursor,
Pd2(dba)3 (dba = dibenzylideneacetone), exhibited extremely high turnover number (TON) of
3.3 x 107 for the coupling of phenyl iodide with phenyl boronic acid.[20]
Pd-NHC complex
R X + R' M R R' + M X
R' M = organoboranes (Suzuki)

organostannanes (Stille)
organomagnesium (Kumada)
organozinc (Negishi)
organosilicon (Hiyama)
amines (Buchwald-Hartwig)
Sceme 5.
R Ad
N R N i-Pr
Br
O N N
N Cl R N Cl Br
O
Ad i-Pr
R
R = 4-Me-C6H4 (23); 4-Et-C6H4 (24); 4-i-Pr-C6H4 (25); R = OMe (28); H (29); F (30) 31
4-Ph-C6H4 (26); 4-OEt-C6H4 (27)
c-hex
c-hex
Cl N
N N
Fe PPh2 NI
t-Bu
c-hex
c-hex
32 33
Figure 3.
It is worth mentioning that catalysts with ultra-high turnover numbers (TONs) are
primarily important from the point of utilizing only little amount of the expensive palladium
metal as well as the N-heterocyclic carbene ligands for the catalysis. The catalysts exhibiting
ultra-high turnover numbers enjoy an additional advantage of avoiding any tedious catalyst
separation step often required at the end of the catalytic cycle and thereby adding to the
overall cost effectivity of the process. Another ferrocenyl phosphine functionalized
imidazolium iodide salt 33 (Figure 3) exhibited a remarkably high turnover number (TON) of
up to 20,000 and a turnover frequency (TOF) of up to 10,000 h-1 for the cross-coupling of aryl
bromides.[21]
Significant breakthroughs have been achieved in the coupling of the more difficult aryl
chloride substrates using N-heterocyclic carbenes. Specifically, a 1,3-dialkylperhydro-
benzimidazolinium chloride salts 23−27[22] and its related unsaturated counterparts,
benzimidazolium chloride salts 28−30[23], (Figure 3) carried out the cross-coupling of aryl
chlorides at a relatively low temperature 80 °C in good to excellent yields. Another sterically
demanding phenanthryl derived N-heterocyclic carbene precursor 32[24] (Figure 3)
performed the cross-coupling of aryl chlorides under ambient conditions i.e., both at room
temperature and at 50 °C. In this regard it is worth mentioning that Buchwald introduced the
use of sterically demanding phosphine ligands for the cross-coupling of aryl chlorides.[25]
Parallel to the “Ligand Assisted Catalysis” (LAC) studies, efforts were directed toward
designing Pd(0) and Pd(II) initiators of N-heterocyclic carbene ligands for the cross-coupling
reaction. The use of well-defined transition metal based initiators is advantageous particularly
with regard to avoiding a large excess of expensive N-heterocyclic carbene ligands often seen
under “Ligand Assisted Catalysis” (LAC) conditions. However, the approach calls for greater
efforts with synthesis and characterization of well-defined discrete catalyst complexes.
Notable are several palladium(0) complexes of N-heterocyclic carbenes having both saturated
and unsaturated imidazole frameworks of type 9−16 (Figure 1) that have been successfully
employed in the Suzuki−Miyaura cross-coupling reaction of aryl chlorides in good to
excellent yields at 3 mol % of the catalyst loading. b,f,h Another bis-oxazoline derived N-
heterocyclic carbene palladium(0) complex 17 carried out the coupling of sterically
demanding 2,6-disubstituted aryl chlorides at a much lower catalyst loading of 0.03 mol %
under ambient conditions in good to excellent yields. c A slight variant of the Suzuki−Miyaura
reaction employing aryldiazonium tetrafluoroborate salts as substrates instead of the
ubiquitous aryl halides was reported using a palladium(0) N-heterocyclic carbene complex 21
at 50 °C. e
In sharp contrast to only a handful of examples known of Pd(0) precatalysts for the cross-
coupling reaction, the Pd(II) counterparts have been extensively studied. The numerous
palladium(II) N-heterocyclic carbene precatalysts that exist can be primarily classified into
four types, (i) the mono-N-heterocyclic carbene complexes (A), (ii) bis-N-heterocyclic
carbene complexes (B), (iii) the PEPPSI (Pyridine Enhanced Precatalyst Preparation,
Stabilization and Initiation) themed complexes (C) and lastly, (iv) the mixed N-heterocyclic
carbene and phosphine complexes (D) (Figure 4).
Among the mono-N-heterocyclic carbene Pd(II) precatalysts, the (NHC)Pd(allyl)Cl types
34−39[26] have been thoroughly studied by carrying out the variation of substituents on the
allyl moiety like in 40−42[27] as well as on the N-heterocyclic carbene ligand like in
47−52[28] (Figure 5). Specifically, the air and moisture stable precatalysts 34−38b showed
high activity towards the cross-coupling of activated and unactivated aryl chloride and
bromide substrates at 60-80 °C in presence of NaOtBu as a base. On the contrary, the
precatalyst 39a was found to be only moderately active in the Suzuki−Miyaura coupling of
aryl halides. The precatalysts, 40−42, possessing different alkyl and aryl substituents on the
allyl moiety, exhibited high cross-coupling activity under ambient conditions at room
temperature. In particular, the precatalyst 42 performed the coupling of a wide range of aryl
bromide, triflate and the chloride substrates with boronic acids at room temperature at an
extremely low catalyst loading of 0.05 mol %. A similar type of naphthyl based
(NHC)Pd(allyl)Cl precatalysts 47−49c performed better than the precatalysts 37 and 38 at 80
°C. Significant reactivity difference could be seen among the precatalysts 47−49 in the
coupling reaction performed at room temperature. Another precatalyst 50b carried out the
coupling of aryl chlorides with 1-naphthalene-boronic acid at a low catalyst loading of 0.2
mol% in a short reaction time of 2 hours at 60 °C.
Figure 4.
i-Pr i-Pr
N N N N N N N N N N
R R R R R R R R
i-Pr i-Pr
Pd Pd Pd Pd Pd
Cl Cl Cl Cl Cl
R R'
R = t-Bu (34); 2,6-i-Pr2C6H3 (35); R = 2,6-i-Pr2C6H3 (37); mesityl (38); R = Me, R' = H (40); R = 2,6-i-Pr2C6H3 (43); mesityl (44) R = 2,6-i-Pr2C6H3 (45); mesityl (46)
mesityl (36) 2-(Ph)C6H4 (39) R = Me, R' = Me (41);
R = Ph, R' = H (42)
X
R'
R O O i-Pr i-Pr
BF4
N N N N N N
N
R Cy2N NCy2 N
OX O i-Pr i-Pr N
Pd Pd Pd Pd
R' Mes Mes
Cl Cl Cl
R = R' = i-Pr (47); X = (CH2)8 (50) R = H (51); Ph (52) 53

R = R' = Me (48);
R = H, R' = Me (49);
Figure 5.
Attempts toward designing mixed cyclopentadienyl and N-heterocyclic carbene systems

of palladium, 43−46[29] proved to be of limited success though these precatalysts performed
the Suzuki−Miyaura cross-coupling of a wide range of substrates including the chlorides in
room temperature. In this regard it is noteworthy that cyclopentadienyl ligands have played a
significant role in olefin polymerization, C−H activation, hydrogen transfer reaction,
hydroamination, hydration of terminal alkynes to aldehydes, asymmetric allylic alkylations,
asymmetric Diels-Alder reaction etc.[30] Several ionic complexes of the types
[(NHC)Pd(allyl)]+BF4-, 53,[31] and [(NHC)PdCl]+X- (X = BF4, PF6 and Cl), 54−58,[32] have
been found to be good for the coupling of aryl chloride, bromide and iodide substrates (Figure
6). The ionic complex 53 showed high activity in carrying out the cross-coupling at low
catalyst loadings of 0.05−0.5 mol %. Another variation includes a series of N-chelated N-
heterocyclic carbene palladium complexes 60−62,[33] 64−66[34] and 69[35] (Figures 6 and
7).
X O
N O N O N
N N N N N
Br N N Fe Pd Cl
N N
N N
Pd Pd Pd Pd Ph
N N
R' Br Cl Cl Cl
Cl N Cl Ph N
N
R = Me, R' = n-Bu, X = BF4 (54); N Ph
R = Me, R' = n-C7H15, X = BF4 (55);
R = Me, R' = n-C7H15, X = PF6 (56);
R = H, R' = n-Bu, X = BF4 (57);
R = Me, R' = mesityl, X = Cl (58); 59 60 61 62
Me
i-Pr
N N N N N
N O
i-Pr S
N i-Pr O N
N Pd
Pd Pd Pd Me
i-Pr O
Cl
N Cl N
(OAc)2 Me N O Cl
Me Me
63 64 65 66
Figure 6.
Of these, notable are the 60, 62 and 69 precatalysts that carried out the Suzuki−Miyaura
cross-coupling at low catalyst loadings. Of special mention is the 60 complex that exhibited
high turnover number (TON) of up to 11,750 for the Suzuki−Miyaura cross-coupling of an
activated p-bromoacetophenone substituent with phenylboronic acid. a The other reported
variations of precatalysts include mononuclear trans-[PdBr2(NHC)(imidazole)] (59)[36] and
dinuclear [(NHC)Pd(μ-X)X]2 (X = halide) type 67,[37] 68[38] and 70[39] complexes, of
which 70 efficiently catalyzed the Suzuki−Miyaura cross-coupling at low catalyst loading
under mild reaction conditions (Figure 7). The precatalyst 63[40] of the type (NHC)Pd(OAc)2
exhibited the cross-coupling of aryl chlorides and activated alkyl chlorides with aryl boronic
acids.
The bis-N-heterocyclic carbene palladium precatalysts primarily fall into two categories
namely, the non-chelated (NHC)2PdX2 (X = halide) and the chelated-(NHC)2PdX2 (X =
halide) type complexes (Figures 8−9). Notable is a non-chelated trans-(NHC)2PdX2 type
complex 71[41] that exhibited ultra high turnover number (TON) of 1,09,600 for the cross
coupling of o-bromobenzaldehyde with phenylboronic acid at 85 °C in 12 hours of the
reaction time. Similar type of non-chelated trans-(NHC)2PdX2 type complexes 72−73[42],
81,[43] 90−91[44] have been designed for the Suzuki−Miyaura cross-coupling of aryl halides
with aryl boronic acids. Specifically, the precatalysts 90−91 performed the coupling reaction
of 4-bromotoluene and phenylboronic acid at low catalyst loadings of 0.002 mol% exhibiting
turnover numbers (TONs) of up to 13,700 at 85 °C in 24 hours. The benzthiazoline derived
precatalysts 74−75[45] having a rare cis-geometry for unbridged non-chelated (NHC)2PdX2
type complexes showed turnover numbers (TONs) of up to 3,300 for the coupling of p-
bromobenzaldehyde with phenylboronic acid.
2 2Cl i-Pr
OMe
n-Bu
R n-Bu N
N N N N
i-Pr N i-Pr Cl
N Br Br N N Cl
R N
R Pd Pd Pd Pd i-Pr Pd Pd i-Pr
Br Br N N Cl
N Cl N i-Pr
N i-Pr
N N
R N N N
n-Bu
OMe n-Bu i-Pr
R = i-Pr (67); CH(Ph)2 (68) 69 70
Figure 7.
Quite interestingly, a 1,2,3-triazole derived abnormal N-heterocyclic carbene trans-

(NHC)2PdX2 type precatalyst 92[46] exhibited the cross-coupling of aryl bromides with aryl
boronic acids. However, the observed activities were not too high. Adding to the structural
diversity, an acyclic chelated diaminocarbene complex of type bis-(NHC)2PdCl2 93[47] has
been reported for the cross-coupling of aryl bromide and chloride substrates with aryl boronic
acids at 1 mol% of catalyst loading.
The chelated cis-(NHC)2PdX2 type of complexes 83−86[48] and 89[49] displayed the
cross-coupling of aryl bromides with phenylboronic acid. Particularly, the o-xylyl-linked
alkoxy benzimidazole precatalysts 83−86 exhibited moderate to high activities, displaying
turnover numbers (TON) of up to 26,000 for the coupling of aryl bromides with
phenylboronic acid. Though chelated bis-(NHC)2PdX2 complexes often exhibit cis-
geometries, unusual trans-dispositions were observed in the case of the 76 and 77 complexes,
in which the two N-heterocyclic carbenes were linked by extended crown-ether linkages.[50]
Quite importantly, the precatalysts, 76−77, showed ultra high turnover numbers (TONs) of up
to 99,000 for the coupling of aryl bromides with aryl boronic acids in neat water under
aerobic conditions. Other chelated bis-N-heterocyclic carbene precatalysts 78−80,[51] 82[52]
and 87−88[53] were found to be active for the cross-coupling of aryl and benzyl halides. The
precatalysts 87−88 performed the cross-coupling of aryl boronic acids with aryl and
arylmethyl bromides in water.
The third category involves PEPPSI (Pyridine Enhanced Precatalyst Preparation,
Stabilization and Initiation) themed precatalysts, which were originally designed with the
intention of having a loosely bound “throwaway” ligand namely, a pyridine moiety, trans to
the metal bound strongly σ-donating N-heterocyclic carbene ligand (Figure 10). The strong
trans effect of the N-heterocyclic carbene ligand was anticipated to weaken the binding of the
diagonally opposite “throwaway” pyridine ligand, which would thus dissociate and give away
to the incoming substrate. Several variations of PEPPSI themed precatalysts bearing non-
functionalized 94−97, e,[54] the N/O-functionalized N-heterocyclic carbene sidearm
substituents 98−112[55] alongwith differently substituted pyridine variants 94−114e, have
been synthesized. Variation on the imidazole ring too has been attempted in the form of
benzimidazole N-heterocyclic carbene PEPPSI precatalysts 113−114. The precatalysts 94−97
showed high activity in the Suzuki−Miyaura cross-coupling of aryl bromide and chloride
substrates with the various boron derivatives like aryl boronic acids and alkyl-9-BBN (9-BBN
= 9-borabicyclo[3.3.1]nonane). Significantly enough, the precatalyst 97a exhibited excellent

catalytic activity in the coupling of sterically hindered aryl bromides and chlorides with aryl
boronic acids to yield bulky tetra-ortho-substituted biaryl products in good yields under mild
reaction conditions. The precatalyst 94b performed the cross-coupling of unactivated alkyl
bromide and the aryl bromide and chloride substrates with alkyl-9- borabicyclo[3.3.1]nonane
at room temperature. The N/O-functionalized N-heterocyclic carbene based PEPPSI (Pyridine
Enhanced Precatalyst Preparation, Stabilization and Initiation) complexes 98−100b were
found to be excellent precatalysts not only for the commonly observed Csp2–Csp2 coupling but
also for the more challenging Csp3–Csp2 cross-coupling at a low catalyst loading of 0.35 mol
%. The PEPPSI precatalysts 101−112 have been reported for the cross-coupling of aryl
chlorides with phenylboronic acids in water at 1 mol % of catalyst loading. Notable are the
N/O-functionalized N-heterocyclic carbene precatalysts 113−114 that exhibited higher
turnover numbers (TON) of up to 4,930 for the coupling of 4-bromotoluene with
phenylboronic acid.
The last category represents the mixed N-heterocyclic carbene and phosphine complexes,
which are primarily of two types namely, the neutral (NHC)PdX2(PR3) and the ionic
[(NHC)PdX(PR3)2]+X- complexes (Figures 11−12). Both normal as well as abnormal N-
heterocyclic carbene precatalysts have been reported for the above two classes. Quite
remarkably, the (NHC)PdX2(PR3) type precatalyst 115[56] showed superior activity
exhibiting ultra-high turnover numbers (TONs) of up to 106 for the aryl bromides and of up to
6,000 for the aryl chloride substrates with phenylboronic acids. The deactivated bromoarenes
could also be efficiently coupled at a low catalyst loading of 0.005 mol %. The other variation
of the (NHC)PdX2(PR3) type precatalysts, 124−131, ,[57] 138−141[58] and 143−151,[59]
have been reported for the cross-coupling of aryl bromide and chloride substrates with aryl
boronic acids. The precatalysts, 124−125, showed high turnover numbers (TONs) of up to
18,300 for the coupling of 4-bromotoluene with phenylboronic acid. The precatalysts
143−146a have been used for the coupling of bulky aryl boronic acids with the aryl bromide
and chloride substrates. A neutral (NHC)PdX2(PR3) type precatalyst of mixed abnormal
pyrazole based N-heterocyclic carbene and phosphine ligands, 132−133 have also been
employed in the cross-coupling reaction.a
The mixed abnormal N-heterocyclic carbene and phosphine complexes of the ionic type
[(NHC)PdX(PR3)2]+X- precatalysts, 116−123, b showed excellent activity for the cross-
coupling of aryl bromide and chloride substrates with phenylboronic acids with the
precatalyst 120 exhibiting ultra-high turnover number (TON) of up to 2,600,000 for the
coupling of p-bromo acetophenone with phenylboronic acid. The pyrazole derived abnormal
N-heterocyclic carbene precatalysts 134−135a were reported for the cross-coupling for aryl
bromides and chlorides with phenylboronic acids in aqueous medium at both room
temperature and at 80 °C. It is interesting to note that the ionic type [(NHC)PdX(PR3)2]+X-
complexes 134−135 are more active than the corresponding neutral (NHC)PdX2(PR3) ones
132−133. A few examples of chelated bis phosphine/phosphite complexes 136−137[60] and
142[61] have been reported for the cross-coupling of aryl and alkyl bromides.
A few more examples of polymer supported precatalysts for the Suzuki−Miyaura cross-
coupling reactions are known,[62] however, these are beyond the purview of the present
chapter that focuses on the utility of N-heterocyclic carbene based palladium complexes in
homogeneous catalysis and biomedical applications.
LnPd(0)
R R' R X
reductive oxidative
elimination addition
R R
LnPd LnPd
R' X
M X R' M R' M = organoboranes (Suzuki)

organostannanes (Stille)
transmetallation organomagnesium (Kumada)
organozinc (Negishi)
organosilicon (Hiyama)
amines (Buchwald-Hartwig)
Scheme 6.
Important is the knowledge of the mechanism of a reaction for the design and discovery
of new catalysts. Of the several views that persist of the Suzuki−Miyaura cross-coupling
reaction, the most commonly accepted one involve a Pd(0)/Pd(II) shuttle in its catalytic cycle
(Scheme 6). The mechanism is proposed to proceed via an active Pd(0) species, often formed
in situ from the reduction of Pd(II) precursors by a base or a phosphine ligand or an organic
nucleophile etc. The electron rich Pd(0) species subsequently undergoes oxidative addition
followed by transmetallation of organic nucleophile from an organoboron reagent. The final
step involves a reductive elimination step yielding the desired cross-coupled product. More
interestingly, the above mechanism has been found to be generic for many similar palladium
catalyzed C−C and C−N cross-coupling reactions (Scheme 6).
Heck−Mizoroki Reaction
The palladium-mediated coupling of aryl and alkenyl iodides, bromides, triflates etc. with
alkenes in the presence of a base is popularly known as the Heck−Mizoroki reaction (Scheme
7). As the name suggests it was first independently discovered by Mizoroki[63] and Heck[64]
in the 1970s. Over the years because of its wide spread utility in complex natural product
synthesis and in industrial processes, the Heck−Mizoroki reaction has grown into an
important C−C cross-coupling reaction. As was the case with Suzuki−Miyaura coupling, here
too, Herrmann first introduced N-heterocyclic carbenes in Heck−Mizoroki reaction in
1995,[65] even three years earlier than that he did the same for in Suzuki−Miyaura coupling
in 1998.
Scheme 7.
Subsequently, several reports of the application of N-heterocyclic carbenes in

Heck−Mizoroki coupling have appeared over the years with many performed under “Ligand
Assisted Catalysis” (LAC) conditions (Figure 13). Notable is a 1,3-bis(mesityl)-imidazolium
chloride salt 152[66] that efficiently carried out the coupling of n-butyl acrylate with
bromoarenes at different palladium to the ligand ratios of 1:1 and 1:2. Another saturated N-
heterocyclic carbene precursor 153[67] performed intramolecular Heck reaction and
decarbonylative Heck coupling. A bis(imidazolium) salt 154[68] was used as an ionic liquid
in presence of PdCl2 for the Heck coupling of aryl halides with n-butyl acrylate. Quite
significantly, a multidentate N-heterocyclic carbene ligand precursor 155[69] exhibited the
coupling of aryl bromides with styrene and t-butyl acrylate. The 1,3-
dialkylperhydrobenzimidazolinium chloride salts 23−27 (Figure 3) performed the coupling of
aryl bromides with styrene in good to excellent yields. A new class of efficient
triphenylarsinyl-functionalized N-heterocyclic carbene based precatalysts 157−159a have
been tested for the Heck, hydro-Heck, π, σ domino-Heck reactions. Furthermore phosphine
functionalized N-heterocyclic carbene ligand precursors, 156[70] and 160−162[71] in
presence of Pd(dba)2 exhibited the Heck coupling of a wide array of aryl bromides and
iodides with n-butyl acrylates in excellent yields.
Though “Ligand Assisted Catalysis” (LAC) was quite successful in the Heck−Mizoroki
coupling, numerous attempts have also been made towards employing well-defined Pd(0) and
Pd(II) complexes in the cross-coupling reaction. It is noteworthy that among well-defined
palladium precatalysts, fewer reports exist of Pd(0) ones. A Pd(0) precatalyst 20i (Figure 1)
performed the Heck coupling of 4-bromoacetophenone with n-butyl acrylate. Another
palladium(0) precatalyst 21e (Figure 1) carried out the coupling of aryl diazonium salts with
various olefinic substrates. However, there exists comparatively a lot more examples of well-
defined Pd(II) precatalysts for the cross-coupling reaction than the palladium(0) ones.
In this regard a variety of the mono-N-heterocyclic carbene Pd(II) precatalysts namely,
53, (Figure 5) 61, c (Figure 6) 69 (Figure 7) and 163−181 (Figures 14−15) have been
designed. Interestingly enough, the precatalysts 163−164, 170a and 179[73] stabilized by
pyridine chelated N-heterocyclic carbene ligands exhibited high activities in the coupling
reaction. Quite remarkably, the precatalyst 164b showed ultra-high turnover numbers (TONs)
of up to 2,858,000 for the coupling of methyl acrylate and iodobenzene. Another precatalyst
181[74] supported over a pyrazole chelated N-heterocyclic carbene ligand as opposed to the
aforementioned pyridine chelated N-heterocyclic carbene ones in the 163−164, 170 and 179
complexes exhibited good activity in an ionic liquid medium of 1-butyl-3-methylimidazolium
hexafluorophosphate, [(BMIm)(PF6)] salt. Along similar line, the pyrimidine chelated N-
heterocyclic carbene precatalysts[75] 66 (Figure 6) and 175−178 (Figure 15) and a pyrazole
chelated N-heterocyclic carbene precatalyst 180[76] (Figure 15) efficiently performed the
Heck−Mizoroki couplings.
A new class of mixed N-heterocyclic carbene-palladacycle precatalysts 165[77] and
171[78] was reported for the cross-coupling reaction (Figure 14). A precatalyst 165 exhibited
very high turnover numbers (TONs) of up to 5,33,000 for the coupling of an activated 4-
bromoacetopheneone substrate with styrene. A highly air and moisture stable precatalyst 171
exhibited good to excellent yields for coupling of functionalized aryl and heteroaryl bromides
and iodides with olefins. Several benzothiazoline based palladium precatalysts 168−169 and
173 showed the high catalytic activity for the coupling of aryl bromides with t-butyl
acrylate.[79] The mixed β-diketonato N-heterocyclic carbene complexes 166−167[80] and an
acetate bridged dimer of the type 174[81] exhibited good cross-coupling activities.
Apart from the mono-N-heterocyclic carbene precatalysts, the bis-N-heterocyclic carbene
ones 182−256 (type B, Figure 4) have been extensively studied for the cross-coupling
reaction (Figures 16−20). Quite interestingly, the precatalyst 187 exhibited the turnover
numbers (TONs) of up to 13,000 after due optimization of the reaction conditions.[82]
Variation of the substituent from a methyl group in 187 to a phenyl group in 188, led to
significant increase in the turnover numbers (TONs) to up to 88,000. Similarly the
precatalysts 203−204 showed high turnover numbers (TONs) of up to 77,000. In this context
worthy of mention are the six-membered cyclic diaminocarbene complexes 182−183[83] that
exhibited extremely high turnover numbers (TONs) of up to 9,97,000 for the coupling of 4-
bromoacetophenone with n-butyl acrylate. A homoleptic palladium precatalyst 205[84]
showed ultra-high turnover numbers (TONs) of up to 8.08 x 108 for the cross-coupling of
phenyl iodide and styrene. The precatalysts 184−186[85] performed the Heck-Mizoroki
coupling of t-butylacrylate and aryl halides. Specifically, a cationic amine tethered bis-N-
heterocyclic carbene precatalyst 184 exhibited the high turnover numbers (TONs) of up to
34,700 in the coupling of t-butylacrylate and 4-bromoacetophenone. A series of palladium
precatalysts 191−201[86] of CNC-pincer ligand containing two N-heterocyclic carbene
moieties connected to a pyridine core showed excellent performance in the Heck–Mizoroki
reactions. A related variant 202c in the form of a CCC-pincer ligand was also found to be
active in the cross-coupling reactions. Quite significantly, the precatalysts 197 and 202 were
found to be thermally stable thereby facilitating the Heck–Mizoroki olefination of aryl
chlorides at a high temperature. c
Several other chelated cis-(NHC)2PdX2 type complexes namely, 83–86, (Figure 8) 89,
(Figure 9) 189–190, (Figure 16) 220–227, a,[87] (Figure 18) 234 (Figure 19) and 243–254[88]
(Figure 20) have been designed as precatalysts for the Heck–Mizoroki C−C cross-coupling
reactions. Of special mention are the o-xylyl linked alkoxy benzimidazole derived
precatalysts 83–86 that showed very high turnover numbers (TONs) of up to 1,800,000 for
the coupling of n-butyl acrylate and iodobenzene. Similar type of o/m-xylyl linked imidazole
derived precatalysts 220–226a, a showed excellent activity for the coupling of aryl halides and
n-butyl acrylate. The N-methylated benzimidazole derived precatalysts 209–216[89]
performed the Heck–Mizoroki arylations of t-butyl acrylate. It is worth noting that both the
cis- 209 and trans- 210 isomers were equally active in the cross-coupling reaction. c The
related cis-carboxylate palladium precatalysts 214–216b showed high activities for the
coupling of aryl halides and t-butylacrylate.
O O
O O
R R' N
Cl N Cl
N N X O O N N
S N N
Pd Pd Pd Pd
N N S N N
X N N
Cl Cl Cl Cl
N N N
R' R R R
Pd
N N
Cl
R = t-Bu, R' = CH22-(OMe)C6H4 (71); R R
R = i-Pr, CH2CONHCH2Ph (72); X = Br (74); O2CCF3 (75) R = mesityl (76); 2,6-i-Pr2C6H3 (77) R = CH2Ph (78); n-Bu (79); 81
R = CH2Ph; CH2CONHCH2Ph (73) CH2mesityl (80)
OBu
BuO
BuO
N N BuO N N
N BuO Br OBu Br
BuO Br BuON N Pd
Pd Cl N N Pd BuO N N Pd
N Br Br Br
N N BuO N N
BuO
OBu
82 5,6-BuO (83); 4,7-BuO (84) 85 86
Figure 8.
R Br
N
N N N
O BuO I OBu
N N N N
N Pd Br Pd Pd
HO Br Br N N
BuO I OBu
N
N R
R = COOEt (87); COOH (88) 89 5,6-BuO (90); 4,7-BuO (91)
Me
H Me
N Ph Boc N Me N N Me
N Cl N N
N H H
Pd Pd
N
Cl Cl Cl
N
N Boc Ph N
Me
92 93
Figure 9.
The chelated cis-(NHC)2PdX2 type 241[90] and the non-chelated (NHC)2PdX2 type
255[91] precatalysts derived from chiral amines exhibited good catalytic activity in the Heck–
Mizoroki arylation reactions. An oxazoline derived trans-(NHC)2PdX2 type precatalyst
235[92] was found to be less active in the cross-coupling reaction. The non-chelated
(NHC)2PdX2 type precatalysts 236–237[93] showed good catalytic activities in double Heck–
Mizoroki coupling reactions with aryl dibromides yielding diacrylates.
R
R R
Cl X Br HOOC
N N N
Pd N Pd N Pd N
N N N
Cl Cl X Br HOOC
R R'
R'
R = 2,6-i-Pr2C6H3 (94); 2,6-Et2C6H3 (95); R = CH2Ph, R' = CH2CONHtBu, X = Cl (98); R = CH2OMe, R' = mesityl (101);
mesityl (96); 2,6-i-pentC6H3 (97) R = 2-(OH)C6H10, R' = CH2Ph, X = Cl (99); R = CH2OMe, R' = 2,3,5,6,-Me4C6H (102);
R = t-Bu, R' = CH22-(OMe)C6H4, X = Br (100) R = CH2OMe, R' = 2,3,4,5,6,-Me5C6 (103)
Br BuO I
N N
Pd N X'' Pd N
N N
Br X X' BuO I Cl
R'
5,6-BuO (113); 4,7-BuO (114)
R = CH2OMe, R' = mesityl, X = COOH, X' = X'' = H (104);
R = CH2OMe, R' = mesityl, X' = COOH, X = X'' = H (105);
R = CH2OMe, R' = mesityl, X'' = COOH, X = X' = H (106);
R = CH2OMe, R' = 2,3,5,6-Me4C6H, X = COOH, X' = X'' = H (107);
R = CH2OMe, R' = 2,3,5,6-Me4C6H, X' = COOH, X = X'' = H (108);
R = CH2OMe, R' = 2,3,5,6-Me4C6H, X'' = COOH, X = X' = H (109);
R = CH2OMe, R' = 2,3,4,5,6-Me5C6, X = COOH, X' = X'' = H (110);
R = CH2OMe, R' = 2,3,4,5,6-Me5C6, X' = COOH, X = X'' = H (111);
R = CH2OMe, R' = 2,3,4,5,6-Me5C6, X'' = COOH, X = X' = H (112)
Figure 10.
The precatalysts of the type (NHC)2Pd(Me)Cl, 206–207a, and 217–219, a, efficiently

performed the cross-coupling reaction in good to excellent yields. Quite remarkably, the
precatalyst 217a showed an extremely high turnover numbers (TONs) of up to 9,80,000 while
a related precatalyst 218 showed up to 1,700,000. Another precatalyst 256 of the
[(NHC)PdCl][PdCl3] type, exhibited turnover numbers (TONs) of up to 1,20,000 and a
turnover frequency (TOF) greater than 4,500 h-1. A dicationic palladium precatalyst 242[94]
showed turnover numbers (TONs) of up to 106 and a turnover frequency (TOF) of up to 5 x
104 h-1 for the coupling of n-butyl acrylate and aryl halide substrates.
The PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation)
themed ones supported over functionalized benzimidazole N-heterocyclic carbenes namely
113–114 exhibited high turnover numbers (TONs) of up to > 1,800,000 for the cross-coupling
of iodobenzene and n-butyl acrylate. Lastly, several mixed N-heterocyclic carbene (NHC)
and phosphine precatalysts namely, 115–123b (Figure 11), 124–125 (Figure 11), 136–141,
(Figure 12) and 257–276,[95] (Figures 21–22), have been employed in the Heck–Mizoroki
cross-coupling reaction. Most of these palladium precatalysts mainly fall into two categories
(i) the cationic [(NHC)PdX(PR3)2]+X- type complexes and (ii) the neutral (NHC)PdX2(PR3)
ones. The palladium complexes 116–123, b 136−137and 257–265a belong to the cationic
[(NHC)PdX(PR3)2]+X- type. Quite significantly, the cationic precatalyst 137 of a N-
heterocyclic carbene derived PCP-pincer ligand showed ultra-high turnover numbers (TONs)
of up to 56,000,000 in the coupling of phenyl iodide with styrene. The other class of neutral
(NHC)PdX2(PR3) type precatalysts include the 115b 124–125, (Figure 11) 138–141 (Figure
12) and 266–268a complexes. Among these, notable is the precatalyst 124 that exhibited
extremely high turnover numbers (TONs) of up to 1,713,000 for the coupling of iodobenzene
and n-butyl acrylate.
BF4 BF4 Me BF4

Me
X' BF4 X' N X N
N N X N
i-Pr i-Pr X Me
Ph3P Pd Cl Ph3P Pd PPh3 Ph3P Pd PPh3 Ph3P Pd PPh3 Ph3P Pd PPh3
Cl Cl Cl Cl Cl
X = NMe, X' = CH (116); X = H, X' = H (118); X = H (121); X = Me (122) 123

115
X = CH, X' = NMe (117) X = Me, X' = H (119);
X = H, X' = Me (120)
OTf
BuO PPh3 L PPh3 PPh3
N S
N N
Pd I Pd Br Pd I Pd I
N N N N
BuO I Br R I R PPh3
R
5,6-BuO (124); 4,7-BuO (125) L = PPh3, R = CH2Ph (126); R = Ph (132); Me (133) R = Ph (134); Me (135)
L = PPh3, R = n-Pr (127);
L = PCy3, R = CH2Ph (128);
L = PCy3, R = n-Pr (129);
L = PPh2Py, R = CH2Ph (130);
L = PPh2Py, R =n-Pr (131)
Figure 11.
Cl 2 2 BF4
N N N N
t-Bu O P(OR)2
I
N
Ph3P Pd PPh2 Ph3P Pd PPh2 Pd PR3 Pd PCy3
N
I Cl
N t-Bu
Cl
C
Me
136 137 R = Ph (138); 2-(CH3)C6H4 (139); Cy (140); t-Bu (141) R = 2,4-t-Bu2C6H3 (142)
O O
Ph N N Ph N N
NHPh NHPh N
Ph
N P
R3P Pd Cl R3P Pd Cl Pd Ph
R
Cl Cl
Cl Cl
R = Ph (143); Cy (144) R = Ph (145); Cy (146) R = mesityl (147); CH2C10H7 (148); CH2Ph (149);CH24-(F)C6H4 (150);
CH23-(OMe)C6H4 (151)
Figure 12.
Scheme 8.
In addition to the large body of palladium precatalysts discussed above there exist a
handful of examples of polymer supported ones for the Heck−Mizoroki cross-coupling
reactionb,d,g,[96] that were employed under heterogeneous catalysis conditions and hence they
fall outside the scope of the present discussion.
The mechanism of Heck–Mizoroki cross-coupling reaction involves the Pd(0)/Pd(II)
states in its catalytic cycle (Scheme 8). The mechanism initiates with an oxidative addition of
an aryl or alkenyl halide on a catalytically active palladium(0) species to generate a
palladium(II) intermediate, which reacts with an olefin to yield a palladium(II) alkyl complex.
The palladium(II) alkyl complex then undergoes β–hydride elimination to form the desired
cross-coupled product. The last step involves the base assisted elimination of HX from the
palladium(II) complex, thus, regenerating the starting palladium(0) active species.
Stille Cross-Coupling Reaction
A convenient protocol for biaryl synthesis alongside the Suzuki−Miyaura and Hiyama
couplings is the Stille reaction that involves a C−C cross-coupling of aryl halides with
organostannens (Scheme 5).[97] However, the reaction’s wide spread utility is largely
plagued by several major limitations like that of the toxicity issues with tin as a metal and the
difficulties associated with removing the metal from the final reaction mixture. The N-
heterocyclic carbenes were first introduced by Herrmann in the Stille coupling in 1999.[98]
Figure 13.
Figure 14.
Figure 15.
Figure 16.
2 2 BF4
N N Me Me
N N N N
X Me X
N N N N
N Pd N Pd Pd
N N Pd
Me I I Me I I N N X N N X
Me Me Cl
N N Me Me
203 204 205 X = H (206); Me (207)
RR
N O R
N N N N Me
N
N N N N O R N Me N
Pd R Pd R Pd Pd
O R
Cl Cl X X N N Cl N
N O R Me
R = Me, X = I, cis (209); R = CH2Ph (217);

R = Me, X = I, trans (210); R = Me (214); CF3 (215); R = CH2Py (218);
208 R = i-Pr, X= I, trans (211); CF2CF3 (216) R = CH2CO2Me (219)
R = i-Pr, X= Br, trans (212);
R = i-Pr, X= O2CCF3, cis (213)
Figure 17.
Figure 18.
Figure 19.
Figure 20.
The mixed N-heterocyclic carbene and phosphine precatalysts 138−141, (Figure 12)
performed the cross-coupling of aryl halides with PhSnBu3 in good to excellent yields. Quite
interestingly so, the addition of a fluoride salt e.g. tetrabutyl ammonium fluoride (TBAF),
activated the organotin reagent towards the transmetallation step via the formation of an
anionic hypervalent stannate intermediate. Several in situ generated palladium precatalysts
obtained from the reaction of the N-heterocyclic carbene ligand precursors, 277−279, (Figure
23) and a metal precursor, Pd(OAc)2, were reported for the coupling of phenyl- or
vinyltrialkylstannanes with non-activated aryl chlorides and bromides.[99] A well defined
PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed
precatalyst 97 (Figure 10) performed for the cross-coupling of a variety of challenging aryl or
heteroaryl halides with thiophene-, furan-, pyrrole-, and thiazole-based organostannanes.[100]
Figure 21.
Figure 22.
The Stille coupling exhibits the same catalytic cycle frequently observed for the other
palladium mediated C−C cross-coupling reactions involving the oxidative addition,
transmetallation and reductive elimination sequences (Scheme 6).[101]
Kumada–Tamao–Corriu (KTC) Cross-Coupling Reaction
The nickel- or palladium catalyzed cross-coupling of organomagnesium compounds, i.e.

the Grignard reagents, with alkenyl and aryl halides or triflates is popularly known as the
Kumada–Tamao–Corriu cross-coupling reaction (Scheme 5). The first cross-coupling of
Grignard reagents with alkenyl or aryl halide substrates using nickel was reported
independently by Kumada and Tamao[102] and Corriu[103] in 1972. Later in 1975,
Murahashi reported the use of a palladium catalyst for the coupling reaction.[104]
The utility of N-heterocyclic carbenes ligands in the Kumada–Tamao–Corriu cross-
coupling was first reported by Nolan[105] in 1999, in which an in situ generated palladium
precatalyst 277 was employed for the coupling of aryl Grignard reagents with aryl halide
substrates. There only exists a handful of examples of well-defined Pd(0) and Pd(II) N-
heterocyclic carbene complexes for the Kumada–Tamao–Corriu cross-coupling reaction. In
particular, a well-defined palladium(0) naphthoquinone complex 21 (Figure 1) performed the
cross-coupling of aryl magnesium bromide with alkyl chlorides under ambient conditions at
room temperature.[106] The mono-N-heterocyclic carbene precatalyst 280 (Figure 24) of the
type [(NHC)Pd(μ-Cl)Cl]2 exhibited high activity for the cross-coupling of aryl chloride
substrates with Grignard reagents. Interestingly, the precatalyst 280 not only showed
functional group tolerance towards nitrogen- and sulfur-based heterocycles but also carried
out the coupling of sterically demanding partners.[107] The PEPPSI (Pyridine Enhanced
Precatalyst Preparation, Stabilization and Initiation) themed precatalysts 94−96 (Figure 10)
and 281 (Figure 24) of the type C (Figure 4) also performed the coupling of more challenging
ortho-substituted and heterocyclic aryl halide substrates with Grignard reagents under
ambient conditions.[108] Quite significantly, the precatalyst 94 performed the coupling even
at a low temperature i.e. at -20 °C. The Kumada–Tamao–Corriu coupling goes through the
commonly observed catalytic cycle of a palladium mediated C−C cross-coupling reaction
(Scheme 6).
Negishi Cross-Coupling Reaction
A rather close variant of Kumada–Tamao–Corriu cross-coupling reaction is the Negishi

reaction that involves the C−C cross-coupling of organozinc reagents with organic halides or
triflates catalyzed by nickel and palladium (Scheme 5).[109] So far only a few examples of
palladium N-heterocyclic carbene mediated Negishi coupling have been reported. An in situ
generated palladium precatalyst formed from the reaction of N-heterocyclic carbene ligand
precursor, 1,3-bis(mesityl)-imidazolinium tetrafluoroborate 282 (Figure 25) and a
palladium(0) precursor, Pd2(dba)3, exhibited low activity for the coupling of a alkyl bromide
with a organozinc reagent in the presence of a stoichiometric amount of N-methylimidazole
(NMI) as an organozinc activator.[110] Another the N-heterocyclic carbene ligand precursor
277 in presence of Pd2(dba)3 exhibited much higher conversions for the coupling of
functionalized alkyl bromides and alkylzinc reagents at room temperature in the absence of
any organozinc activator like that of N-methylimidazole (NMI).[111] A well-defined
palladium precatalyst 94 efficiently carried out the coupling of alkyl or aryl halides and
sulfonates with alkylzinc bromide or arylzinc chlorides at room temperature in the presence
of LiCl or LiBr as an additive.[112] The catalytic cycle of Negishi coupling resembles that of
the Kumada–Tamao–Corriu coupling reaction (Scheme 6).[113]
Figure 23.
Figure 24.
Figure 25.
Hiyama Cross-Coupling Reaction
The Hiyama coupling[114] is a palladium mediated C−C cross-coupling of organosilanes

with aryl, alkenyl, or alkyl halides or pseudohalides (Scheme 5). In terms of utility, this
reaction is similar to the Suzuki–Miyaura and the Stille couplings, available for the
construction of biaryl frameworks, but differs by using relatively inert organosilicon
nucleophiles that require an activating agent like a fluoride ion or a base for the coupling to
occur. The low cost, easy availability, environmentally benign nature, reagent stability and
the functional group tolerance of the organosilicon reagents make Hiyama coupling an
enticing option in organic synthesis. A major challenge however lies in enhancing the
nucleophilicity of the inherently inert organosilicon reagents that arise out of very less
electronegativity difference existing between Si and C atoms.[115] In this regard various
anionic activators like F-, OH- and OR- have been effectively used to increase the
nucleophilicity of the organosilicon reagent by facilitating coordination of the activating
anion to the silicon center and thereby resulting in a more nucleophilic anionic penta-
coordinated organosilicon reagent.
Quite surprisingly, the utility of N-heterocyclic carbenes in Hiyama coupling has severely
lagged behind than the other contemporary palladium catalyzed C−C cross-coupling
reactions. A N-heterocyclic carbene ligand precursor 277 in presence of Pd(OAc)2 under
“Ligand Assisted Catalysis” (LAC) conditions performed the coupling of aryl bromides and
chloride substrates with PhSi(OMe)3 in presence of a fluoride coinitiator.[116] A well-defined
mono-N-heterocyclic carbene palladium precatalyst 66a showed high activity towards the
cross-coupling of PhSi(OMe)3 with aryl chloride and bromide substrates in presence of
tetrabutyl ammonium bromide (TBAF) as a fluoride coinitiator. The now-popular PEPPSI
(Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) themed precatalysts
of the type trans−(NHC)PdX2(pyridine) 283−288[117] (Figure 26) based on both the
imidazoline 283−286 and 1,2,4-triazole 287−288 derived N-heterocyclic carbenes efficiently
catalyzed the Hiyama coupling of a wide variety of aryl halides with organosilicon reagents
like PhSi(OMe)3 and (CH2=CH)Si(OMe)3 under fluoride-free conditions but instead using
inexpensive OH− anion as an anionic activator.
The Hiyama coupling too follows the commonly observed palladium mediated C−C
cross-coupling mechanistic pathway (Scheme 6). The fluoride anion or the base present in the
reaction medium activates the organosilicon reagent thereby making it more amenable for
transmetallation.
Sonogashira Cross-Coupling Reactions
The palladium mediated coupling of terminal alkynes with aryl or vinyl halides is
popularly called the Sonogashira coupling (Scheme 9)[118] and as the name suggests it was
first reported by Sonogashira and Hagihara in 1975. The Sonogashira cross-coupling provides
a direct and convenient access to conjugated “enyne” and “arylalkyne” skeletons common in
many natural products, agrochemicals, pharmaceuticals and engineered materials.[119] The
most widely accepted Sonogashira protocol relies on using Cu salts as co-catalysts in a basic
medium usually provided by amines.
Figure 26.
Scheme 9.
The Sonogashira coupling calls for stringent anaerobic conditions as the trace amounts of
oxygen or even an oxidizing environment can yield unwanted homo-coupled products by
Glaser coupling.[120] The air and moisture sensitivity of Sonogashira coupling primarily
arises due to the formation of a Cu−acetylide intermediate under the catalysis conditions.
Thus, achieving Cu-free condition is a key challenge confronting Sonogashira coupling today.
The use of N-heterocyclic carbenes in Sonogashira coupling was also first reported by
Herrmann in 1998. Subsequently the various reports have appeared of the application of N-
heterocyclic carbenes in Sonogashira coupling. A N-heterocyclic carbene ligand precursor
278 in presence of [(π-allyl)PdCl]2 performed the coupling of alkyl bromide and iodide
substrates with terminal alkynes.[121] Another interesting example is the coupling of
trimethylsilylalkynes with deactivated bromoarenes and chlorobenzene by a in situ generated
catalyst from reaction of the N-heterocyclic carbene precursor 152 (Figure 13) and
Pd(OAc)2.[122]
Several palladium well-defined precatalysts have been designed for the Sonogashira
coupling. Quite significantly, a mono-N-heterocyclic carbene bound precatalyst 290[123]
carried out the coupling of bromo- and iodoarenes with terminal acetylenes in the presence of
CuI and PPh3 (Figure 27). Another palladium precatalyst 291[124] performed the Sonogashira
coupling under analogous conditions. Interestingly enough, a palladium precatalyst 289 of a
bioxazoline-derived N-heterocyclic carbene ligand catalyzed the coupling of primary and
secondary alkyl halides with alkynes.[125] The precatalyst 289 showed excellent
chemoselectivity and functional group tolerance in the cross-coupling reaction. The palladium
precatalyst of the type (NHC)PdX2 292[126] and of the type (NHC)2PdX2 293−296[127],
efficiently carried out the coupling of a wide variety of aryl bromides and iodides with
terminal acetylenes (Figure 27).
Figure 27.
Particularly, the precatalysts 293−294performed the Sonogashira coupling under amine

free conditions whereas the precatalysts 292, 295−296 did the same under both the Cu-and
amine-free conditions. The PEPPSI themed precatalysts 283−288 (Figure 26) and
297−303[128] (Figure 27) were also active for the Sonogashira coupling of aryl bromides and
iodides.
Quite interestingly, the precatalysts of the type (NHC)2PdX2, 293−294, showed higher
activity compared to the (NHC)PdX2(pyridine) type ones, 98 (Figure 10) and 297, (Figure 27)
under analogous conditions. The higher conversions observed for the (NHC)2PdX2 type
precatalysts 293−294 thus upholds the hypothesis that more electron rich metal centers act as
better catalysts presumably by facilitating the aryl halide oxidative addition step. Along the
same line of thought, the trans−(abnormal-NHC)PdX2(pyridine) type palladium precatalyst,
300−303[128] (Figure 27) supported over the more σ−donating imidazo[1,2-a]pyridine based
abnormal N-heterocyclic carbene ligands exhibited superior activity than those based on the
normal N-heterocyclic carbene ligands. It is worth noting that the abnormal N-heterocyclic
carbenes by virtue of the carbene center being adjacent to a single heteroatom as opposed to
two heteroatoms in the case of normal N-heterocyclic carbenes are more electron rich and
hence more σ-donating than the normal N-heterocyclic carbenes.
The proposed mechanism for the Sonogashira coupling in presence of a copper cocatalyst
involves two independent cycles i.e., (i) one for the production of the Cu-acetylide species
and (ii) the other for its coupling with the desired aryl or alkyl species (Scheme 10). The
transmetallation of copper acetylide to palladium is believed to be the rate-determining step.
The above mechanism is, however, ruled out in the case of the Cu-free Sonogashira coupling,
for which the coupling proceeds via a commonly observed Pd(0)/Pd(II) shuttle involving
oxidative addition of aryl halide to a palladium(0) active species followed by coordination
and deprotonation of alkynes in the presence of a base, and which subsequently leads to the
desired Sonogashira product by a final reductive elimination step (Scheme 11).
Scheme 10.
Arylation Reaction
The palladium N-heterocyclic carbene mediated arylation reaction observed in the

literature can be classified into the following types.
(I). Arylation of Enolates

The arylation of enolates is a powerful strategy for synthesizing a variety of high-value
chemicals like, α-arylated ketones, esters, nitriles and amides from simple aryl halides. A
handful of examples of N-heterocyclic carbenes in arylation of enolates have been reported.
The enantiomerically pure imidazolium triflates 304−306[129] (Figure 28) in presence of
palladium precursors like Pd(OAc)2 or Pd2(dba)3 have been employed in the synthesis of
oxindoles by asymmetric α-arylation of amides.
Scheme 11.
Scheme 12.
The reaction though proceeded in excellent yields but exhibited low enantioselectivity
(Scheme 12). Other N-heterocyclic carbene precursors, 153 and 277, in presence of Pd(OAc)2
have been used in the inter- and intra molecular α-arylation of amides.[130] Interestingly, a
sterically demanding 1,3-di-(1-adamantylmethyl)-substituted saturated N-heterocyclic
carbene precursor 307[131] in presence of Pd(OAc)2 carried out the α-arylation reaction
enantioselectively showing high enantiomeric excess (ee) but low yields. In this regard
notable is a series of well-defined mono-N-heterocyclic carbene precatalysts 314−316[132]
(Figure 28) that exhibited high ee and high yields in the asymmetric α-arylation of amides. A
bis-(NHC)2PdX2 type precatalyst 320 (Figure 20) has been reported for α-arylation of amides.
Mono-N-heterocyclic carbene palladium precatalysts of the type (NHC)Pd(allyl)Cl
34−37[133] (Figure 5) and 313 and the palladacycle 64[134] (Figure 6) performed the
arylation of simple ketones with non-activated aryl chlorides, bromides, iodides, and triflates
in the presence of NaOtBu (Scheme 13). The arylation occurred at the α-position to the
carbonyl group with preference for the less sterically hindered carbon atom in case of the
unsymmetrical ketones. Along the same line, another close variant of the type
(NHC)Pd(acac)Cl, 317−318,[135] was effective for the α-arylation of ketones.
O O
Pd-NHC complex
+ X Ar Ar
R R
R' R'
Scheme 13.
Scheme 14.
Scheme 15.
(II). Direct Arylation Reactions

Direct arylation reaction is an important method for constructing biaryl frameworks. The
utility of N-heterocyclic carbenes in the direct arylation reaction has thus attracted attention
lately. Notable is the precatalyst 312[136] (Figure 28) that showed high activity for the
intramolecular direct arylation with aryl chlorides (Scheme 14). The use of N-heterocyclic
carbene ligands as additives led to significant enhancement of reactivity, probably due to the
preventive effect on catalyst decomposition at high reaction temperatures. These conditions
allowed the formation of five- and six-membered rings bearing ether, amine, amide, or alkyl
tethers.
Another interesting method for the o-arylation of benzaldehyde derivatives was reported
with the in situ generated palladium precatalyst from the reaction of N-heterocyclic carbene
precursors 279, (Figure 23) and 308−311[137] with Pd(OAc)2. More interestingly, the mono-
ortho-substituted products were formed for the aryl chlorides while di-ortho-substituted
products were observed for aryl bromides.
The direct arylation of alkynes with aryl halides provides another convenient alternative
to biaryl skeletons (Scheme 15). In this regard the well-defined precatalysts 319 and 321−330
(Figure 29) efficiently performed the arylation of alkynes with aryl halide substrates. a,[138]
The other well-characterized precatalysts that include the PEPPSI (Pyridine Enhanced
Precatalyst Preparation, Stabilization and Initiation) themed precatalysts, 321 and 322, and
the mixed N-heterocyclic carbene and phosphine precatalysts, 323−330, carried out the direct
arylation alkynes with phenyl halides. The mixed N-heterocyclic carbene and phosphine
precatalysts 323−330 exhibited the superior activity compared to the PEPPSI themed ones
321−322 of the type (NHC)PdCl2(pyridine) and also to the (NHC)2PdCl2 type 319 precatalyst
for the direct arylation of alkynes with aryl halides. a
Ph Ph
O O
Ph Ph
N N N N
i-Pr i-Pr Cl Cl
N N N N
Pd I Pd I Pd N Pd N
Ph Ph N N
Cl Cl i-Pr i-Pr Cl Cl
N N
Ph Ph
O O
319 320 321 322
2 2 BF4
Ph
R' N N
N N
PL3
N N PL3 N N
R2P Cy2P
R Pd Ph Pd Pd Pd
X X Cl Cl I I
N N
R = CH2Ph, R' = CH2CONHPh, X = Cl, L = Cy (323);

R = R' = CH2Ph, X = Cl, L = Ph (324); L = Ph (326); Cy (327) R = Ph (328); Cy (329) 330
R = R' = CH2Ph, X = Br, L = Ph (325)
Figure 29.
Hydroarylation Reactions
Hydroarylation of alkynes is a highly atom economic protocol that makes use of

inexpensive starting materials like arenes. Fujiwara first reported the reaction of simple
arenes with alkynes in trifluoroacetic acid (TFA) yielding stilbenes catalyzed by
Pd(OAc)2.[139] Later, the N-heterocyclic carbene based palladium precatalysts 63 (Figure 6)
and 331 (Figure 30) have been employed for the hydroarylation of ethyl propiolate that
produced stilbene derivatives at room temperature (Scheme 16).[140] Another efficient
precatalyst 332 exhibited high activity along with high chemo- and stereoselectivities for the
hydroarylation of alkynes at a low catalyst loading of 0.1 mol %[141].
Figure 30.
COOEt
O Pd-NHC complex
+ +
OEt R
R COOEt
COOEt
R
Scheme 16.
C−N Bond Formation Reaction
The palladium mediated C−N bond forming reactions are fundamentally important to
organic synthesis like the C−C cross-coupling ones and these reactions mainly are of two
types (i) the Buchwald–Hartwig amination reaction (Scheme 5) and (ii) the hydroamination
reaction (Scheme 17). Due to its wide spread applicability, atom economy, and the product
value, the C−N bond forming reaction are of great importance to both industry and academia.
Scheme17.
Buchwald−Hartwig Amination Reaction
First discovered independently by Buchwald[142] and Hartwig[143] in 1995, the

Buchwald−Hartwig reaction involves the coupling of aryl halides, triflates and tosylates with
aryl or alkyl amines, amides, sulfonamides, imines, nitrogen-containing heterocycles and
ammonia. The palladium precatalysts of bulky tertiary phosphines are often used in this
transformation.[144] As the N-heterocyclic carbenes are often regarded as the “phosphine
substitutes” their utility in the C−N bond forming reaction is increasingly becoming popular.
The N-heterocyclic carbene precursor 277[145] in presence of Pd2(dba)3 exhibited good to
excellent conversions for the amination of aryl chlorides, bromides and iodides. Interestingly,
an N-heterocyclic carbene precursor 277 in presence of Pd2(dba)3 carried out the amination of
aryl chlorides with benzophenone imine.[146] The more electron rich N-heterocyclic carbene
precursor [153] performed the N-arylation of indoles. Several other N-heterocyclic carbene
precursors 333−337 (Figure 31) have been reported for the amination reaction. b,[147] Quite
significantly, the N-heterocyclic carbene precursor 333 in presence of Pd(dba)2, showed
turnover numbers (TONs) of up to 5,000 for the amination of aryl chlorides. b The in situ
generated bisimidazol based precatalysts, obtained from the reaction of 333−334 with
Pd2(dba)3, were successfully employed in coupling 7-azabicyclo[2.2.1]heptane with aryl and
heteroaryl chlorides and bromides. a
Figure 31.
Several well-defined palladium(0) and palladium(II) precatalysts have been employed for
the Buchwald−Hartwig amination reaction. The palladium(0) precatalysts 10−11 (Figure 1),
15−16b (Figure 1) and 346[148] (Figure 32) have been reported for the amination reactions of
aryl chloride substrates. Specifically, the precatalyst 15 and a mixed N-heterocyclic carbene
and phosphine palladium(0) precatalyst, 346, showed excellent conversions for the amination
reactions of aryl chlorides with the primary, secondary and arylamines. Contrary to the fewer
reports of well-defined palladium(0) complexes that exist, the palladium(II) counterparts have
been rather extensively studied. In this context several mono-N-heterocyclic carbene
palladium(II) precatalysts 35, b 37, b 52a (Figure 5), 64 (Figure 6), 70[149] (Figure 7),
338−340[150] and 341−345[151] (Figure 31) have been reported for the amination reaction.
Quite significantly, the cinnamyl complexes 52a and 345 showed excellent activity in the
Buchwald−Hartwig amination. The precatalyst 345 efficiently carried out the amination
reactions of a wide range of unactivated, neutral and activated chlorides and bromides with a
variety of primary, secondary, alkyl, or arylamines at room temperature. The palladium alkyl
derivatives 341−342a were effective in the Buchwald−Hartwig amination reaction of aryl
chlorides. The air and moisture stable precatalysts 317−318 (Figure 28) and 70 exhibited
excellent activities for the amination of aryl chlorides and bromides with a variety of amines
under mild conditions.
Figure 32.
The N-heterocyclic carbene-palladacycles 343−344b showed Buchwald−Hartwig

amination for a range of unactivated aryl chloride substrates.
Quite remarkably, the PEPPSI (Pyridine Enhanced Precatalyst Preparation, Stabilization
and Initiation) themed precatalyst 94 (type C, Figure 4) was effective for the amination
reaction of electron-deficient, electron-rich aryl and heteroaryl chlorides and bromides with
various sterically hindered and also functionalized drug-like aryl amines.[152] The mixed N-
heterocyclic carbene and phosphine precatalysts 265 (Figure 21) and 347−349 (Figure 32)
were found to be active for the amination reaction of bromobenzene or 2-chloropyridine with
morpholine. a
The catalytic cycle proposed for the Buchwald−Hartwig amination reaction is analogous
to that of the other palladium mediated C−C cross-coupling reactions like, Suzuki–Miyaura,
Hiyama, Stillle, Negishi and Kumada-Tamao-Corriu couplings involving a common
Pd(0)/Pd(II) cycle.[153] The catalysis originates with the oxidative addition of aryl halide or
pseudohalide to a palladium(0) active species followed by the coordination of the amine to
the metal. Subsequently, the palladium bound coordinated amine undergoes deprotonation in
the presence of a base. Finally, the reductive elimination step yields the amine product with
the regeneration of palladium(0) active species (Scheme 6).
Hydroamination Reaction
Another important and also atom economic C−N bond forming reaction is the
hydroamination reaction that involves the formal addition of a N−H bond across a C−C
multiple bond (Scheme 17). Hydroamination is sometime weakly exergonic or thermoneutral
and therefore exhibits a very high negative entropy of the reaction making it
thermodynamically less favorable.[154] In this context the transition metal catalyzed
hydroamination reaction assumes relevance as it facilitates catalytic C–N bond formation
under amenable conditions with controlled chemo-, regio- and stereoselectivities and
functional group tolerance.[155]
BF4
2 2BF4 2 2BF4
Ph N N t-Bu N N
N N R
N Pd H N Pd NCMe R' N MeCN Pd NCMe

O t-Bu
i-Pr R
MeCN
t-Bu N N t-Bu N N
350 351 R = t-Bu, R' = CH2Ph (352);

R = mesityl, R' = H (353)
2 2PF6
i-Pr R N N Fe
Br
N N N
Pd Fe P Pd P
R2 R2
N N N
Br
R i-Pr NCCH3
R = Et (354); CH2-CH=CH2 (355) R = Ph (356); R = 3,5-(Me2)C6H3 (357)
Figure 33.
The utility of N-heterocyclic carbenes in the hydroamination reaction has received much
less attention so far. In this regard significant a the mono-N-heterocyclic carbene precatalyst
350[156] (Figure 33) that carried out the hydroamination of methacrylonitrile with piperidine.
Other well-defined palladium precatalysts 351−353 of the type bis-(NHC)2PdX2 have been
reported for the hydroamination of methacrylonitrile with secondary amines. A new class of
palladium precatalysts 354−355[157] of 1,2,4-triazole derived N-heterocyclic carbenes
showed moderate to good conversions for the hydroamination of activated olefins under
ambient conditions . Lastly, for the asymmetric hydroamination of methacrylonitrile with
aliphatic amines, the mixed N-heterocyclic carbene and phosphine precatalysts,
356−357,[158] exhibited high yields but low enantiomeric excess (ee).
Oxidation Reaction
The oxidation reactions exhibited by palladium N-heterocyclic carbene complexes are

mainly of the following two types,
(i). Oxidation of Alcohols

Palladium(II) catalyzed oxidation of alcohols using molecular oxygen as an oxidant is a
very useful transformation in organic synthesis (Scheme 18).[159] The use of palladium
precatalyst of N-heterocyclic carbene in an oxidation reaction was first reported by Sigman in
2003.[160] The precatalyst 312 carried out the oxidation of a variety of benzylic and allylic
alcohols to the corresponding aldehydes and ketones exhibiting turnover numbers (TONs) of
up to 1,000. b Along the same line, the precatalysts 358−359[161] (Figure 34) performed the
aerobic oxidation of alcohols. Quite significantly, Stahl[162] isolated rare peroxo and
hydroperoxo derivatives of palladium that are important intermediates in the oxidation
catalysis. A detailed theoretical study on these complexes revealed that the solvent plays an
important role on the reversibility of the oxygenation step. c
The oxidation reactions using molecular oxygen as terminal oxidants have been
successfully applied for the kinetic resolution of secondary alcohols and to the alkene
hydroarylation reaction employing boronic esters (Scheme 19). Specifically, the chiral
palladium precatalysts 360−362[163] showed oxidative kinetic resolutions of secondary
alcohols in good yields with moderate to good enantioselectivities. The precatalysts 280[164]
carried out highly regioselective reductive coupling of arylboronic esters and styrene under
aerobic conditions. In this reaction, the oxidative conditions are required for the oxidation of
the alcoholic solvent to generate the active palladium(II) hydride intermediate, which reacts
with alkene to yield a palladium alkyl species. Subsequent transmetallation and reductive
elimination yield the desired product (Scheme 17).
OH O
Pd-NHC complex
R R' R R'
Scheme 18.
(II). Wacker Oxidation and Oxidative Cyclization Reactions

Palladium catalyzed oxidation of terminal olefins to methyl ketones is popularly known
as the Wacker oxidation and is used in the production of acetaldehyde on an industrial
scale.[165] In this process stoichiometric CuCl2 is used as a cocatalyst under aerobic
conditions.
i-Pr i-Pr Ph
N N R
N N
Ph N N N Me
Me
i-Pr i-Pr N Cl Cl
R I I
O Pd O R Pd Pd Pd Pd
N I I
R R Cl Cl
Ph N Me N Me
O O N N N
R
Ph
R = 2,3,5,6-Me4C6H (360) 361 362

R = Me (358); t-Bu (359)
Figure 34.
Scheme 19.
However, the reaction suffers from many drawbacks like the formation of chlorinated
byproducts and from the issues associated with palladium decomposition. These have
contributed to the growth of research in the area. Notable is a precatalyst 70 (Figure 7) that
performed the oxidation of styrenes to acetophenones (Scheme 20).[166] An in situ generated
precatalyst derived from the N-heterocyclic carbene ligand precursor 152 and palladium
bistrifluoroacetate Pd(COOCF3)2 exhibited efficient intramolecular Wacker-type cyclization
reaction under aerobic conditions (Scheme 21).[167]
Reduction Reaction
An in situ generated palladium precatalyst obtained from the reaction of N-heterocyclic

carbene precursor 279[168] with Pd(dba)2, performed the dehalogenation of aryl bromides
and chlorides at 100 °C (Scheme 22). In this transformation the formation of a cationic
palladium hydride intermediate is proposed and which is formed from the oxidative addition
of a imidazolinium salt to a palladium(0) precursor species. Another well-defined complex 35
(Figure 5) of the type, [(NHC)Pd(allyl)Cl], have been reported for the dehalogenation of aryl
chlorides. b
A cationic bis-N-heterocyclic carbene precatalyst 363[169] carried out the hydrogenation
reaction of cyclooctene to cyclooctane (Scheme 23). A mixed N-heterocyclic carbene and
phosphine palladium(0) precatalyst 5 (Figure 1) of the type (NHC)Pd(PR3) performed the
hydrogenation of olefins.[170]
Scheme 20.
R'
Pd-NHC complex R
R O2, toluene, 80 oC O R'

OH
Scheme 21.
Scheme 22.
Pd-NHC complex
1 atm H2
i-Pr
2 2 BF4
N
N NCMe
Pd
N NCMe
N
i-Pr
363
Scheme 23.
Tsuji-Trost Alkylation Reaction
Palladium catalyzed allylic substitution reaction has become a popular method of C−C
bond formation along the lines of various other C−C cross-coupling reactions. Quite
interestingly, though a palladium mediated allylic substitution reaction was reported by Tsuji
in 1965,[171] the use of N-heterocyclic carbene in allylic alkylation reaction was only
reported as late as in 2003.[172] An N-heterocyclic carbene precursor 277 (Figure 23) in
presence of Pd2(dba)3 was found to be active for the allylic alkylation reaction (Scheme
24).[172,173]
Telomerization Reactions
(I). Telomerization of Dienes with Alcohols

Telomerization is a 100 % atom economic process involving the formation of short
oligomers from dienes. The palladium complexes are known to catalyze the reaction of dienes
with a variety of nucleophiles.[174] Beller first employed a mono-N-heterocyclic carbene
palladium(0) complex 18d (Figure 1) for the telomerization of butadiene with alcohols
(Scheme 25). Quite remarkably, better chemoselectivity in terms of linear to branched
product ratios were observed for the N-heterocyclic carbene precatalyst than the phosphine
ones.
(ii). Telomerization of Dienes with Amines

Like the telomerization of dienes and alcohols, the telomerization of amines and dienes is
also an interesting transformation for the formation of short oligomers. Nolan first employed
a well-defined cationic palladium(II) percatalyst 364[175] for the telomerization of butadiene
with amines under mild conditions (Scheme 26). The order of amine reactivity in the
telomerization reaction was found to be as, secondary amines > primary amines > ammonia.
Polymerization Reactions
The use of palladium N-heterocyclic carbene complexes in polymerization reactions are

relatively less explored compared to the other catalysis. The precatalysts 365−377 (Figure 35)
have been employed in a variety of polymerization reactions. In particular, the mono-N-
heterocyclic carbene complex 365[176] performed the norbornene polymerization exhibiting
very high activitiy of up to 108 g of polynorbornene (mol of Pd-1 h-1) in the presence of
methylaluminoxane (MAO) as a coinitiator. Other mono-N-heterocyclic carbene precatalysts
35, 40, 42 (Figure 5) and 366−367 carried out the polymerization of functionalized
norbornene namely, 5-norbornene-2-methyl acetate.[177] Along the same line, the
precatalysts 35−36[178] and 368−370 and the bis(aryloxide-N-heterocyclic carbene)
precatalysts 373−377[179] performed the polymerization of norbornene and its derivatives.
The cationic bis-N-heterocyclic carbene precatalysts 371−372[180] have been reported for the
copolymerization of CO and C2H4.
Scheme 24.
OMe
Pd-NHC complex
2 + MeOH +
OMe
Scheme 25.
Pd-NHC complex
+ RR'NH NRR'
2
i-Pr i-Pr PF6

N N
i-Pr i-Pr
Pd
NCMe
364
Scheme 26.
Cycloisomerization Reactions
The transition metal-catalyzed cycloisomerization of enyne systems is a powerful

synthetic approach for the construction of intricate architectures in various target
molecules[181]. A handful of examples of N-heterocyclic carbenes in the cycloisomerization
reaction have been reported. Of particular mention is an N-heterocyclic carbene precursor
336,[182] which in the presence of Pd2(dba)3, carried out the bismetalative cyclization of
enynes in the presence of Bu3SnSiMe3 (Scheme 27).
2 2X
i-Pr i-Pr R R
N N N N N N
N N R
Me
X X N
i-Pr i-Pr R R
N Pd Pd Pd MeCN Pd
N
Cl Cl
Cl Cl
NCMe R
X
PhPh
R = Me, X = Br (368); R = mesityl, X = PF6 (371);

365 X = H (366); Me (367) R = i-Pr, X = Br (369);
R = i-Pr, X = I (370) R = Me, X = BF4 (372)
t-Bu t-Bu t-Bu
t-Bu N N t-Bu N
t-Bu
O N O O N
R N
Pd R Pd Pd t-Bu
N R
O R O O
N N t-Bu
t-Bu N t-Bu N N t-Bu
t-Bu
t-Bu t-Bu
R = Ph (373); mesityl (374) R = Me (375); i-Pr (376) 377
Figure 35.
Figure 35.
A mono-N-heterocyclic carbene complex 367[183] (Figure 35), of the type

(NHC)Pd(allyl)Cl, was employed for the cycloisomerization of 1,6-dienes forming various
cyclic compounds. Quite significantly, the cycloisomerization reactions proceeded at room
temperature with complete regioselectivity yielding the desired exo-methylene-containing
products (Scheme 28). Another precatalyst 378[184] was reported for the cycloisomerization
of alkylidenecyclopropanes that resulted in the corresponding 1-aryl dihydronaphthalenes in
very high selectivity at room temperature (Scheme 29).
Scheme 27.
Figure 28.
R
R
Pd-NHC complex
R Mes Mes R
Cl
N N
Pd
N N
Cl Mes
Mes
378
Scheme 29.
Addition Reactions
Designing highly efficient and enantioselective palladium N-heterocyclic carbene

precatalysts remain an important goal in asymmetric synthesis. In this regard notable are the
chiral precatalysts 379−380[185] (Scheme 30) that performed the asymmetric conjugate
addition of arylboronic acids to cyclic enones in good to high enantioselectivities. The same
precatalysts 379−380[186] were also employed for the allylation of aldehydes with
allyltributyltin, CH2=CH-CH2SnBu3 (Scheme 31).
A mixed N-heterocyclic carbene and phosphine precatalyst 381[187] was employed for
the conjugate allylation reaction of α,β-unsaturated N-acylpyrroles using allylboronic ester
(Scheme 32). An in situ generated palladium precatalyst formed from the reaction of the N-
heterocyclic carbene precursor 152 with Pd(OAc)2, was reported for the 1,4-addition of
terminal alkynes to unsaturated carbonyl compounds (Scheme 33).[188]
A thioether functionalized N-heterocyclic carbene precursor 382 [189](Scheme 34) in
presence of [Pd(allyl)Cl]2 performed the 1,2-addition of boron reagents to aldehydes. A 1,1′-
binaphthalenyl-2,2′-diamine (BINAM) palladium precatalyst 383[190] (Scheme 35) was
reported for the arylation of N-tosylimines with arylboronic acids in good to high
enantioselectivities. Finally, a triazolyldiylidene derived palladium complex 384[191]
(Scheme 36) was reported for the direct acylation of aryl iodides or bromides with aldehydes.
O O
Pd-NHC complex
+ ArB(OH)2
*
Ar
O
N N
Me
O R
Pd
O R
N Me
N O
R = Me (379); CF3 (380)

Scheme 30.
OH
Pd-NHC complex
RCHO + SnBu3
R
Scheme 31.
O Me O Ar
Me O Pd-NHC complex
N Ar B N
+
Me O
Me
Cl
N PPh2
Pd
N
Me
381
Scheme 32.
O
O Pd-NHC complex R'
R +
R' R
Scheme 33.
O OH
Pd-NHC complex
+ [B] R'
R H R R'
i-Pr
Cl
N N
i-Pr PhS
382
Scheme 34.
Ts Ts
N Pd-NHC complex NH
ArB(OH)2 +
R Ar R
2 2OTf
N N
OH2
Pd
OH2
N
N
383
Scheme 35.
O O
R Pd-NHC complex R
X +
R' H
R'
Me Me
Cl N N Cl
Pd N Pd
MeCN NCMe
Cl Cl
Me
384
Scheme 36.
R R R R RR
Pd-NHC complex
OH OH
+ R' H O
X
R' R'
Me Me
Cl N N Cl
Pd N Pd
N N
Cl Cl
Me
385
Scheme 37.
Scheme 37.
Domino Reactions
There exist only a few reports of domino reactions involving sequential C−C bond
forming reactions catalyzed by palladium N-heterocyclic carbene complexes. Notable is a
palladium N-heterocyclic carbene complex 385[192] (Scheme 37) that was successfully used
for the domino Sonogashira and hydroalkoxylation reactions. Another precatalyst 94
catalyzed the synthesis of indoles by sequential aryl amination and Heck coupling reactions
(Scheme 38).[193]
Scheme 38.
Palladium in Biomedical Application
Metallopharmaceuticals are emerging as prominent players in therapeutic and diagnostic

medicine these days. Hence, the discovery and development of new metallodrugs is an
increasingly popular area of research in medicinal inorganic chemistry in recent times.[194]
Among the commonly used metallodrugs today are cisplatin, cis-(NH3)2PtCl2, and its second
generation analog, carboplatin.[195] However, there exist several concerns with these
metallodrugs like its effect on narrow spectrum range of cancer cells, low aqueous solubility,
various toxicity issues in the form of nephrotoxicity, neurotoxicity and emetogenesis that
constrict its broad based utility.[196] Hence, finding suitable alternate metallodrugs remains a
key objectiveat the heart of research in this area. Palladium as a metal display similar
structural preferences like platinum and also exhibit promising cytotoxicity and thus provides
a viable alternative to the platinum based metallodrugs like cisplatin and carboplatin.[197]
Moreover, the N-heterocyclic carbenes, though extremely successful in catalysis, remain
largely unexplored in biomedical applications. Against this backdrop, the palladium
complexes of N-heterocyclic carbenes 386−388,[198] (Figure 36) were screened for their
anticancer properties. Particularly interesting is the trans-(NHC)2PdX2 type 387 complex that
was found to be more effective than not only a trans-(NHC)PdX2(pyridine) type 386 complex
but also exhibited ca. 2-20 times greater inhibition on the proliferation of the three different
commonly occurring human tumor cells namely, the cervical cancer (HeLa), breast cancer
(MCF-7) and colon adenocarcinoma (HCT 116) cell lines than the much used metallodrug
cisplatin under analogous in vitro conditions. The superior activity of the palladium N-
heterocyclic carbene complex 387 compared to the commonly used metallodrug, cisplatin,
further brightens the prospects of the N-heterocyclic carbene compounds in cancer therapy.
Detailed mechanistic studies revealed that the 387 complex arrested the cell cycle at the
G2/M transition phase of the cell division.
CONCLUSIONS
In summary, the palladium N-heterocyclic carbene complexes have made an indelible
mark in chemical catalysis and are displaying promising traits in biomedical applications like
in anticancer studies. In this context the success of N-heterocyclic carbene primarily arises
due to their strong binding nature, that prevents catalyst leaching by suppressing ligand
dissociation, and thus provides an ideal platform for designing palladium catalysts with
improved attributes as well as for synthesizing palladium compounds for biomedical

application purposes.
t-Bu t-Bu Mes Mes

Cl Cl Cl
N N N N N
Pd N Pd Pd
N N N N N
Cl Cl Cl
t-Bu Mes Mes
386 387 388
Figrue 36.
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Chapter 14
METHODS FOR ENHANCING THE ACTIVITY

AND SELECTIVITY OF HOMOGENEOUS CATALYSTS
IN THE OXIDATION PROCESSES *
Ludmila I. Matienko, Larisa A. Mosolova

and Gennady E. Zaikov
Emanuel Inst. of Biochemical Physics,
Russian Academy of Sciences, Moscow, Russia
The application of metal-complex catalysis opens the possibility of regulating the relative
rates of elementary stages Cat–O2, Cat–ROOH, Cat–RO2 and in that way of controlling the
rate and selectivity of processes of radical-chain oxidation [4]. By changing the ligand
environment of the metal center or adding different activating compounds, it is possible to
vary the yields of target products, and thus control the reaction selectivity.
The catalyst performance is always accompanied by its deactivation. It should be
mentioned that in its original form, a catalyst often represents only the precursor of real
catalytic particles. By introducing various ligands-modifiers into reaction, it is possible to
accelerate the formation of catalytically active species and prevent or hinder the processes
that lead to catalyst deactivation. Understanding of the mechanisms of the additive’s action at
the formation of catalyst active forms and mechanisms of regulation of the elementary stage
of the radical-chain oxidation may apparently lead to the development of new, efficient
catalytic systems and selective oxidation processes.
In heterogeneous catalysis, the methods of modifying a catalyst by different additives that
enhance its activity and prevent its deactivation were used rather extensively, whereas in
homogenous catalysis, the use of various modifiers was not systematic. Studies aimed at
investigation of the mechanism of action of additives were scarce. They were basically aimed
at studying the effect of added ligands-modifiers on catalyst activity in chain initiation steps
*
A version of this chapter was also published in Selective Catalytic Hydrocarbons Oxidation: New Perspectives, by
Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov, Nova Science Publishers. It was submitted
for appropriate modifications in an effort to encourage wider dissemination of research.
464 Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov
(the O2 activation, ROOH homolytic decomposition) [4, 7]. Moreover, in the majority of
schemes of catalytic radical-chain oxidation of hydrocarbon, the O2 activation with transition
metal complex was totally ignored.
The additives, often being axial ligands for metal complexes, are considered in models,
which mimic enzyme reaction center (mono- and dioxygenase). At present, the numerous
examples of various catalytic reactions are known when addition of certain compounds in
small amounts dramatically enhances the reaction rate and rarely the product yield. As a rule,
the mechanisms of action of additives were not established, although the authors tentatively
propose mechanistic explanations [9].
The works of Ellis and Lyons, and more recently that of Gray and Labinger, have
identified the halogen-substituted metal porphyrins—catalyzed oxidation of alkanes into
alcohols by dioxygen at the mild conditions (100oC) [10-13]. However, substituted alkanes,
such as 2-methylbutane, 3-methylpentane, 2,3-dimethylbutane, and 1,2,3-trimethylbutane, are
oxidized into a mixture of products due to oxidative carbon-carbon bond cleavage [11].
The including of halogen, electron-withdrawing substituents, into porphyrin ligand
increases the stability of halogenated iron porphyrins in oxidative destruction and as result
their activity [10, 11]. Though observed to increase, the stability of such complexes remained
moderate, as indicated by the low conversion of alkanes. It is now generally agreed that one-
electron redox reactions and oxygen-centered free radical chemistry being about the
oxidations in these systems are most probably the mechanisms similar to those proposed for
biological oxidations by Cytochrome P-450 and methanemonooxygenase (through two-
electron oxygen-transfer processes at participation of an active high-valent metal-oxo
oxidant) [12,13,14]. Perhalogenated iron porphyrins are known to be effective at
decomposing alkyl hydroperoxides via free radicals formation [13,14].
III.1. IMMOBILIZATION OF HOMOGENEOUS CATALYST ON

HETEROGENEOUS SUPPORT FOR INCREASE IN ACTIVITY
AND SELECTIVITY OF CATALYST IN THE ALKYLARENS OXIDATIONS
Several studies were devoted to the processes of alkylarene oxidation in the presence of
metal complexes immobilized on the surface of a polymer or mineral carrier (silica gel,
zeolite) [15-21].
The potential advantages of using a solid catalyst include the case of its removal from the
oxidation mixture and subsequent reuse and control of catalyst reactivity through its
microenvironment exerted by the support. For example, metal complexes, heterogenised in
the zeolite pores, are prevented from deactivation; the oxidation of the ligand by another
complex cannot be realized. The increase in stability encapsulated salen complex arises from
the protection of the inert zeolite framework, making complex degradation more difficult by
sterically impeding the attack to the more reactive parts of the ligand, and the life of salen
catalyst is prolonged [16]. At the same time, the zeolite influences the formation of products
by steric and electronic influences on the transition state of the reaction; they also control the
entry and departure of reagents and products. One of the limitations of zeolites are that their
tunnel and pore sizes are no larger than about 10 Ǻ [18]. The occluded catalytic complexes
require a zeolite with caves or intersections, which are large enough to embed them. For these
Methods for Enhancing the Activity and Selectivity… 465
purposes, faujasites, containing super cages, are most frequently used [16]. The creation of
mesopores in zeolite particles to increase accessibility to the internal surface has been the
subject of many studies (mesopore-modified zeolites). It is known that postsynthesis
hydrothermal dealumination and other chemical treatments form defect domains of 5 to 50
nm (which are attributed to mesopores) in faujasites, mainly zeolite Y [16].
The low activity of these zeolite catalysts is connected with their high hydrophility, as a
result of low silicon to aluminum ration. The deactivation by sorption of polar products and
solventы on pores of zeolite still remained a serious issue for oxidation of alkanes (with low
polarity). Even with dealumination of the structure up to a silicon to aluminum ratio above
100, increased the activity only twice [16]. The creation of a hydrophobic environment
around the active site was required to circumvent the activity and sorption problems.
In the case of the reaction of cyclohexane oxidation to adipic acid with air in the presence
of Fe –aluminophosphate-31 (ALPO-31) (with narrow pore, 0.54-nm diameter), cyclohexane
is easily adsorbed in the micro pores [18]. But desorption of initial products such as
cyclohexylperoxide or cyclohexanone is slow. Consequently, subsequent radical reactions
occur until the cyclohexyl ring is broken to form linear products that are sufficiently mobile
to diffuse out of the molecular sieve. In contrast, with a large pore Fe – ALPO-5,
cyclohexanol and cyclohexanone account for ~ 60% of the oxidation products. Thus,
localization of a free radical reaction inside micro pores seems to give rise to particular
selectivity.
Often, the catalytic activity is practically unchanged if supported metal complex is used.
So the silica—and polymer—supported iron(III) tetrakis(pentafluorophenyl)porphyrins,
FeTF8PP, [17] catalyzed the ethylbenzene oxidation reactions by dioxygen into the same
three products, α-phenylethyl-hydroperoxide, methylphenylcarbinole, and acetophenone
(1:1:1), as analogous homogeneous catalyst. This suggests the same reaction mechanism in
both cases that these catalytic oxidations react by the same mechanism. However, in general,
the heterogeneous catalytic ethylbenzene oxidation proceeds more slowly than homogeneous.
The products yields are limited by the stability/activity ratio of iron porphyrin and these, in
turn, are dependent mainly on catalyst loading and microenvironment provided by support.
The “neat” and zeolite-Y-encapsulated copper complexes with tri- and tetraaza
macrocyclic ligands such as 1,4,7-triazocyclononane, 1,4,7-trimethyl-1,4,7-
triazocyclononane, 1,4,7,10-tetraazocyclododecane, 1,4,7,10-tetramethyl-1,4,7,10-
tetraazocyclododecane, and 1,4,8,11-tetraazocyclotetradecane exhibit efficient catalytic
activity in the regioselective oxidation of ethylbenzene using tert-butyl hydroperoxide [20].
Acetophenone was the major product; the small amounts of o- and p-hydroxyacetophenones
were also formed, revealing that C–H activation occurs at both the benzylic and aromatic ring
carbon atoms. The latter is significant over the “neat” complexes in the homogeneous phase,
while it is suppressed significantly in the case of the encapsulated complexes. Molecular
isolation and the absence of intermolecular interactions (as revealed by EPR spectroscopy),
synergism due to interaction with the zeolite framework and restricted access of the active site
to ethylbenzene are the probable reasons for the differences in activity/selectivity of the
encapsulated catalysts. The differences in selectivity are attributed to the formation of
different types of “active” copper–oxygen intermediates, such as side-on peroxide, μ-η2:η2-
peroxo (bis-μ-oxo complexes), μ-1,2-peroxo- and Cu-hydroperoxo species, in different
proportions over the “neat” and encapsulated complexes (A−C species):
It [21] is established that with an anisole-containing polypyridylamine, potential ligand

°L, a μ-1,2-peroxodicopper(II) complex [{°LCuII}2(O22-)]2+ forms from the reaction of the
mononuclear compound [CuI(°L)(MeCN)]B(C6F5)4 (°LCuI) with O2 in no coordinating
solvents at -80°C. Thermal decay of this peroxo complex in the presence of toluene or
ethylbenzene leads to rarely seen C-H activation chemistry; benzaldehyde and acetophenone/
1-phenylethanol mixture (~1:1), respectively, are formed. Very similar toluene oxygenation
chemistry occurs with dicopper(III)-bis-μ-oxo species [{BzLCuIII}2(μ-O2-)2]2+ [see Chapter
VII].
Water soluble catalysts combining the properties of metal complexes and surfactants on
the basis of terminally functionalized polyethylene glycols (PEG) and block-copolymers of
ethylene oxide and propylene oxide with various combinations of ethylene and propylene
oxide fragments were investigated [22]. Polymers, functionalized by dipyridyl and acetyl
acetone, were used as ligands for preparation Co(II) complexes. Macro complexes PEG-acac-
Co turned out to be more active than their non-polymeric analogues in oxidation of
ethylbenzene by dioxygen under the same temperature (120°C). The only product was
acetophenone. Cobalt remains fixed at the end of the polymer chain with acac-ligand and is
surrounded by oxygen atoms of the PEG chain. Such surrounding is labile and does not
preclude from activation of dioxygen.
The activity of the liquid-phase polyhalogenated metalloporphyrins (Co, Mn, Fe) and
supported catalysts (silica, polystyrene) and the cationic metalloporphyrins encapsulated in
NaX zeolite are founded to be active for cyclooctane oxidation with molecular O2 into ketone
and alcohol with primary ketone formation. In the last case, the ration c-one/c-ol is higher
than in the use of supported on silica and polystyrene catalysts and, in fact, coincide with
results, which are received with the cationic metalloporphyrins in solution. [23].
Mononuclear ruthenium complexes are catalysts for numerous reactions in solution,
including oxidation, C−C bond formation, and activation of CO2 and C−H bonds.
Dealuminated zeolite Y was used as a crystalline support for a mononuclear ruthenium
complex synthesized from cis-Ru(acac)2(C2H4)2. It was established that in the presence of
ethylene and H2 surface-bound catalytic active mononuclear cationic Ru(acac)(C2H4)22+
complex entered into a catalytic cycle for ethylene dimerization, aided by H2. The cationic
Ru(acac)(C2H4)22+ complex, formed as result of the dissociation of half of the acac ligands
from the ruthenium, was bonded to sites where acidic silanol groups had been presented [24].
III.2. MODIFICATION OF METALLOCOMPLEX CATALYSTS

BY ADDITION OF MONODENTATE AXIAL LIGANDS
The phenomenon of a substantial rise of not only initial rate (w0), but also the selectivity
(S = [PEH] / Δ[RH]·100%) and conversion degree (C = Δ[RH] / [RH]0·100%) of alkylarens
(ethylbenzene, cumene) oxidation to the corresponding hydroperoxides by molecular O2 upon
addition of electron-donating monodentate ligands L2 (L2 = HMPA (hexamethylphosphorus
triamide), dimethyl formamide (DMF), N-methyl pyrrolidone-2 (MP)), MSt (M = Li, Na, K)
to transition metal complexes М(L1)n (M = Ni(II), Co(II), Fe(III), L1=acac-) was discovered
by authors of the articles [25-27].
The mechanism of control of M(L1)2 complexes catalytic activity by adding electron-
donating monodentate ligands L2 (L2 = HMPA, DMF, MP, MSt) in the process of
ethylbenzene oxidation (120°C) was elucidated [28-31].
The coordination of exo ligand L2 to an M(L1)2 changes symmetry of complex and its
oxidative-reductive activity. In that the catalytic activity of the in situ formed in situ primary
complexes M(L1)2·L2 (catalyst K1), containing ligands L2 in axial position is higher than that
of original complexes Ni(L1)2, which is manifested in the acceleration of free radical
formation in the steps of chain initiation (activation by O2) and homolytic decomposition of
α-phenyl ethyl hydroperoxide (PEH), and increase in initial oxidation rate (I macro stage)
[60,61]. In this connection at the first macro stage, the selectivity of ethylbenzene oxidation
into PEH is not high (SPEH,max = 80%). With process development, the increase in SPEH
(SPEH,max ≈ 90%) in comparison with I macro stage, and decrease in reaction w, are observed
(II macro stage). Ligands L2 control transformation of Ni(L1)2 complexes into more active
selective particles (catalyst K2). In that, the rise in SPEH is reached at the expense of catalyst
participation in activation reaction of O2, and inhibition of chain and heterolytic
decomposition of PEH. Besides this, the direction of formation of side products,
acetophenone (AP) and methylphenylcarbinol, (MPC), is changed from consequent (under
hydroperoxide decomposition) to parallel at the expense of modified catalyst in the chain
propagation (Cat + RO2•→). At the III macro stage, the sharp fall of the SPEH is associated
with heterolysis of PEH to phenol and acetaldehyde, catalyzed by the completely transformed
catalyst (catalyst K3) [29-31].
K1 ⎯→ K2 ⎯→ K3
We have established that in the case of use of nickel complexes Ni(L1)2 (L1=acac¯),
selective catalyst K2 (II macro stage) is formed, as result of controlled by L2 ligand regio-
selective addition of O2 to nucleophilic carbon γ-atom of one of the ligands L1. Coordination
of electron-donor exo ligand L2 with Ni(L1)2 stabilized the intermediate zwitter-ion
L2(L1M(L1)+O2¯) and increased the probability of regio-selective insertion of O2 to
acetylacetonate ligand activated by coordination with nickel(II) ion. The further incorporation
of O2 into chelate cycle, accompanied by proton transfer and bonds redistribution in formed
transition complex leads to break of cycle configuration with formation of (OAc-) ligand,
acetaldehyde, and elimination of CO (Scheme 1-3) [29,31]. As a result of this process,
reactive mono- and hetero-poly nuclear heteroligand complexes of general composition
Nix(acac)y(L1ox)z(L2)n (L1ox= MeCOO-) (K2, "А") are formed. Transformation of complexes
K1, Ni(acac)2·L2 (L2 = HMPA, DMF, MP, MSt)) leads to formation of homo bi- (L2 =
HMPA, DMF, MP) or hetero-three nuclear (L2 = MSt, M=Na, Li, K) heteroligand complexes
K2 ("А"): Ni2(OAc)3(acac)L2 (Scheme 1) [29,31]. The structure of the complex "A" with L2
=MP (HMPA) was confirmed kinetically and using various physicochemical methods of
analysis (mass-spectrometry, electron and IR-spectroscopy, and element analysis).
Scheme III.2.1.
Scheme III.2.2.
Transformation of Ni(L1)2 (L1=enamac-, chelate group (O/NH)) is realized in the absence

of activating ligands (L2) [30] (L1ox=NHCOMe- or MeCOO-) (Scheme 2) by analogy with
reactions of oxygenation imitating the action of L-tryptophan-2,3-dioxygenase [32, 33].
Scheme III.2.3.
The principle scheme of oxygenation of ligand (acac)¯ in complex with Ni(II), initiated
with exo ligand L2.
Similar change in complexes' ligand environment as a consequence of acetylacetonate
ligand oxidative cleavage under the action of O2 was observed in --reactions catalyzed of the
only known-to-date a Ni(II)-containing dioxygenase – acireductone dioxygenase, ARD [34]
and its models [35]. This applies to the functional enzyme models, namely, Cu(II)- and
Fe(II)-containing quercetin 2,3-dioxygenases, which catalyze the decomposition of β-

diketones in the enol form to carbonyl compounds with CO evolution. [36, 37].
The similarity of kinetic dependences in the parent processes of ethylbenzene oxidation

in the presence of {Fe(III)(acac)3+L2} (L2=DMF) and {Ni(II) (acac)2+L2} (L2=DMF, HMPA)
(120°C) make it possible to assume that transformation of in situ formed Fe(II)(acac)2·DMF
complexes, into more reactive selective catalytic species could also be a result of ligand L2-
controlled regioselective addition of O2 to the γ-C atom of acetylacetonate ligand [38].
However, the favorable combination of the electronic and steric factors that operate during
the inner- and outer-sphere (hydrogen bonding) coordination of DMF ligand to Fe(II)(acac)2
may promote the acetylacetonate ligand oxygenation by another route realized in the action of
Fe(II) acetylacetone dioxygenase (Dke 1). In this case, oxygen adds to C−C bond (rather than
inserts into the C=C bond as in the catalysis with nickel(II) complexes with consequent
breakdown of cycle configuration through Criegee mechanism) to afford intermediate “B”,
i.e., an Fe complex with a chelate ligand containing 1,2-dioxetane fragment. The process is
completed with the formation of the (OAc)⎯ chelate ligand and methylglyoxal as the second
decomposition product of a modified acac-ring (Scheme 4) [39].
Scheme III.2.4.
The principle scheme of dioxygen-dependent conversion of 2,4-pentandione catalyzed by

acetyl acetone dioxygenase Fe(II).
As in the case of catalysis by Ni complexes in the ethylbenzene oxidation, catalyzed by
Fe(II)(acac)2·L2 complexes, the reactive selective transformation products are polynuclear
hetero ligand complexes with the hypothetical structure:
Fe(II)x(acac)y(OAc)z(L2)n (L2=DMF) [26,38].
The final product of the Fe(II)(acac)2 conversion is the complex Fe(OAc)2, which (as and
Ni(OAc)2) catalyze heterolytic decomposition of PEH to phenol and acetaldehyde (Scheme
4). It is the formation of the completely oxidized form of Fe(OAc)2 catalyst that is responsible
for the sharp drop of selectivity SPEH in the third macro stage [26, 29, 38].
We established that the mechanism of the ethylbenzene oxidation (1200C), catalyzed

Fe(III)(acac)3 in the absence of the activating ligand L2 at rather high value of [Cat] (>5·10-3
mole/l) is changed. The MPC becomes the major product of oxidation, SMPC,0 ≈ 50%. AP and
MPC are produced not parallel, but AP is the product of MPC oxidation. Phenol, as
acetophenone and methyl phenyl carbinol and PEH, is produced at the maximal rate from the
very beginning of the reaction. The change of the catalysis mechanism may be due to
variation in the reactivity of iron complexes. The transformation of Fe(III)(acac)3 into new
catalytically active species, presumably, Fe(II)(acac)2–Q, is proposed. The radical Q, which
can result from the oxidation of the ligand (acac)¯ with Fe(III) ion, is stable and inactive as an
initiator of free-radical oxidation reactions [38]:
It was shown by us that this transformation is negligible in the concentration range of

[Cat] ≤ 5·10-3 mole/l, which was used in our researches (see below). The transformation of the
nascent Q(L1)2)Fe(II) complexes into more active selective catalyst of the hypothetical
structure Fe(II)x(acac)y(OAc)z(Q)n during the Fe(III)(acac)3 – catalyzed ethylbenzene
oxidation most likely follows the described above mechanism (Scheme 4).
The enzymatic cleavage of C-C bonds in β-diketones has growing significance for
various aspects of bioremediation, biocatalysis, and mammalian physiology, and the
mechanisms by which this particular cleavage is achieved are surprisingly diverse [42],
ranging from metal-assisted hydrolytic processes [42] to those catalyzed by dioxygenases
[41]. Carbon monoxide, one of the products of (acac)¯ - ligand oxygenate breakdown path,
catalyzed with the only known-to-date an Ni(II)-containing dioxygenase-acireductone
dioxygenase, ARD, and releasing at the oxygenation of Ni(L1)2·L2 (Scheme 1-3), previously
considered biologically relevant only as a toxic waste product, is now considered a candidate
for a new class of neural messengers [41].
The established mechanism of catalysis of the system {Ni(L1)2+L2}, including the in situ
formation of the prime complexes Ni(L1)2·L2 and following the Ni(L1)2·L2 oxygenation to
more active selective catalysts, allow the solution to the problem of improving of catalyst of
the selective oxidation.
Introduction of Activating Additives in the Course of Catalyzed Oxidation Process

The formation of the active catalyst in the second macro stage of ethylbenzene oxidation
catalyzed by the {Ni(II)(acac)2+L2} system was proved by us from the effect of the
introduction of a fresh portion of Ni(II)(acac)2 complex in the stage of a well-developed
process [33]. A method of affecting a chemical reaction not only in its initial stages but also
in subsequent stages of the fully developed process is an effective way of optimizing complex
multi-stage oxidation processes [8, 29].
It was established by us earlier that at the relatively low nickel catalyst concentration in
the absence of L2, the selectivity of the ethylbenzene oxidation into PEH, catalyzed by
Ni(L1)2 (1,5·10-4 mol/l), was sufficiently high: SPEH,max = 90%. But the growth in SPEH,max is
not accompanied the growth in the conversion C. The value C into PEH in the ethylbenzene
oxidation, catalyzed by Ni(L1)2 (1,5·10-4 mol/l), did not exceed C = 2-4% [29,30].
For an increase of conversion degree of oxidation at maintaining of SPEH,max not less than
90%, the method of catalytic system activation in developed oxidation process was used [8].
In the case of introduction of Ni(II)(acac)2 into ethylbenzene, oxidation reaction catalyzed by

{Ni(II)(acac)2(1.5·10-4 mol/l)+HMPA(1.0·10-3 mol/l)} catalytic system the maximum
possible conversion degree C, at which reaction selectivity is not less than SPEH = 90% is
significantly increased (by a factor of ∼ 3) (Figure 1) [8, 29].
Figure III.2.1. Dependences of selectivity of ethylbenzene oxidation into PEH (SPEH) on conversion
level of ethylbenzene (CPEH) in the presence of system {{Ni(II)(acac)2 +HMPA} without admixtures (1)
and with 4.5·10-4 mol/l Ni(II)(acac)2 (2) added in the course of the oxidation. [Ni(II)(acac)2]0=1.5·10-4
mol/l, [HMPA]=1.0·10-3 mol/l, 120°С.
A prerequisite for the catalyst reactivation is introduction of additives at the instant the
reaction reaches its steady-state mode with respect to SPEH (SPEH = SPEH,max). If additional
amounts of catalyst were added in the moments corresponding to decrease in oxidation
selectivity (SPEH < SPEH,max at C < 4% and C > 5-6%), no reactivation of catalytic system
occurred.
Mechanism of activation consists in increase of steady-state concentration of catalytically
active complex "A" (see Scheme 1) responsible for selectivity of oxidation process.
Activation proceeds in two stages:
1. The fast exchange interaction of the primary complex Ni(acac)2·L2 with Ni(OAc)2
complex was formed during the ethylbenzene oxidation to afford a heteroligand
complex Ni(acac)(OAc)·L2:
Ni(II)(acac)2·L2 + Ni(II)(OAc)2 ⎯→ Ni(II)(acac)(OAc)·L2 (1)
2. The second step is the regioselective oxygenation of the latter to form a binuclear
Ni2(acac)(OAc)3·L2 complex ("А").
Ni(II)(acac)(OAc)·L2 + O2 ⎯→ Ni2(acac)(OAc)3·L2 (2)
Activation of catalytic system {Ni(II)(acac)2+L2} by acacH additives testifies to favor of

exchange interaction between Ni(II)(acac)2·L2 and Ni(II)(OAc)2 (1). However, in this case,
the degree of conversion CS=90% increased to the lesser extent as compared with the addition
of Ni(acac)2 to this system, which was attributed to the oxidation of uncoordinated
acetylacetone acacH [8].
The role of the second stage (2) in catalyst activation, namely, in the formation of a
binuclear nickel complex, was proved by introducing electron-withdrawing additives.
We have found [29] that the simultaneous addition of a fresh portion of Ni(II)(acac)2 and
also a π-acceptor E (tetracyanethylene (TCE) or chloranil (CA)) into {Ni(II)(acac)2+L2}
catalytic system did not increase the degree of conversion CS=90%. The passivation of catalytic
system upon the introduction of TCE or CA can be rationalized as follows: since electron
affinity is increased in the raw О2(0.87) <CА(1.3) < TCE(1.6, 2.2), π-acceptors TCE and CA
electrophylicaly attack acetylacetonate ligand by γ-С-atom stronger than O2 forming out-
spherical complexes and thus preventing the O2 addition by this bond and the formation of a
reactive binuclear heteroligand complex.
The appearance of new absorption in the electronic spectra of the mixtures
{Ni(II)(acac)2+MP+E} as compared with the spectra of E and {Ni(II)(acac)2+MP} testify to
the complexes with charge transfer CTC L2Ni(II)(acac)2•E favor. The outer-sphere reaction of
connection of E to γ-C atom of acetylacetonate ligand is followed by the formation of
L2Ni(II)(acac)2•E [8,29].
The increase in CS=90% does not take place in the case of the introduction of a fresh
portion Co(II)(acac)2 in the ethylbenzene oxidation, catalyzed by {Co(II)(acac)2+ HMPA}
system) unlike the results, received at the ethylbenzene oxidation, catalyzed by
{Ni(II)(acac)2+L2}. At the introduction of a fresh portion of Co(II)(acac)2 to the ethylbenzene
oxidation, catalyzed by Co(II)(acac)2 without additives, the increase in CS=90% occurs. In that,
the conversion CS=90% increases from 5 to 9%. These results seems to be due to the another
mechanism of transformation of the primary complexes Co(II)(acac)2·L2 to more reactive
selective catalyst. The possible mechanism includes the reaction of Co(II)(acac)2·L2 with
peroxide radicals with formation of catalytically active complexes of the probable structure
[Co(III)(L1)2·L2·(RO2¯)] [8] (see below, Chap.III.3).
III.3. MODELING OF TRANSITION METAL COMPLEX CATALYSTS

UPON ADDITION OF AMMONIUM QUATERNARY SALTS AND MACRO-
CYCLE POLYETHERS AS LIGANDS-MODIFIERS.
THE ROLE OF HYDROGEN-BONDING INTERACTIONS
Quaternary ammonium salts are well-known as cationic surfactants. In aqueous solution,
amphiphilic molecules of these salts aggregate to micelles and at higher concentrations to
lyotropic (typical member is CTAB, cetyltimethylammonium bromide) (or thermotropic)
mesophases. Besides this, quaternary ammonium salts are used as phase-transfer catalysts and
as ionic liquids (ILs) in the synthesis of nanosized catalysts [42-46].
As was shown earlier, in various catalytic reactions that occur in water- organic medium,
quaternary ammonium salts R4NX can play two different roles. These salts can act as
catalysts of phase transfer, but also R4NX salts are often directly involved in catalytic reaction
itself. Thus, for example, in reactions of the oxobromination of aromatic compounds a
lipophylic ammonium salt transfers H2O2 into the organic phase. At the same time, since it is
a Lewis acid, it forms R4NBr(Br2)n or R4NBr(HBr)n adducts, thus activating Br2 or salts of
HBr for electrophilic attack on the aromatic ring [44]. In the catalytic oxidation of styrene to
benzaldehyde by H2O2 in water-organic solvent systems ammonium salts completely transfer
H2O2 and catalyst (Ru, Pd) into the organic phase by forming hydrogen bonds. Moreover, the
complex formation affects the properties of the catalyst by the changing of its activity (rate
and selectivity of the reaction) [45]. In the oxidation of p-xylene in a water-organic system in
the presence of CoBr2 and R4NBr, the catalytically active species are complexes CoBr2 with
R4NBr [46]. It is known also that the catalytic activity of CTAB in the ROOH decomposition
in the presence of metals compounds is dependent on structural changes in the formed inverse
micelles [47, 48].
The ability of quaternary ammonium salts to complex formation with transition metals
compounds was established. It was proved, for example, that М(acac)2 (M=Ni, Cu) form with
R4NX (X=(acac)-, R=Me) complexes of [R4N][М(acac)3] structure. Spectral proofs of
octahedral geometry for these complexes were obtained [49]. Complexes Me4NiBr3 were
synthesized and their physical properties were studied [50].
The selective complexation ability of crown ethers is among their most attractive
properties. Crown ethers are also of interest in biologically modeling of enzyme catalysis and
as phase transfer catalysts [43, 51]. Intermolecular and intramolecular hydrogen bonds and
other noncovalent interactions are specific in molecular recognition [51].
Interest in the study of structure and catalytic activity of nickel complexes (especially
nickel complexes with macrocycle ligands) has increased recently in connection with the
discovery of nickel-containing enzymes [52-53]. The latter is the already mentioned Ni(II)-
containing dioxygenase ARD [34]. It is established that active sites of urease are binuclear
nickel complexes containing N/O-donor ligands. Cofactor of oxidation-reduction enzyme
methyl-S-coenzyme-M-reductase in structure of methanogene bacteria is tetra-aza-
macrocycle nickel complex with hydrocorfine Ni(I)F430 axially coordinated inside of enzyme
cavity. [NiFe]-hydrogenase, with an Ni(III) complex in active site. Superoxide dismutase
contains a catalytic cycle Ni(II) ⇔ Ni(III).
To date, the incorporation of transition metals into the cavities of macrocycle polyether
was confirmed by different physicochemical methods; moreover, the specific structure of
resulting complexes is determined not only by the geometric compatibility between the metal
atom and the crown-ether cavity, but also by the whole ensemble of electron and spatial
factors induced by the metal atom, the polyether, the other ligand and also the solvent [54].
The ability of the quaternary ammonium salts as well as macrocycle polyethers to form
complexes with transition metals compounds was used by us in designing new effective
catalytic systems for ethylbenzene oxidation to α-phenylethy hydroperoxide.
Catalysis by Ni(L1)2 in the Presence of Ligand-modifiers L2
It was established by us earlier that the selectivity of the ethylbenzene oxidation into
PEH, catalyzed by Ni(L1)2 at the relatively low nickel catalyst concentrations (≤1,5·10-4
mol/l), was sufficiently high: SPEH,max ≥ 90%. This fact may be expected from the analysis of
the scheme of catalyzed oxidation, including participation of catalyst (Cat=M) in chain
initiation under catalyst interaction with ROOH (1’) and under interaction RH with O2 (1’’,
2), in chain propagation (Cat + RO2•→) (2’) and assuming the chain decomposition of ROOH
(4) and quadratic chain termination reaction (5) (Scheme III.3.1). The precipitation Cat in the
chain propagation (2’) makes it possible to explain the dependence of [ROOH]max and the
maximal rate on catalyst concentration. In this case, the rate of reaction should be decreased,
and [ROOH]max should be increased with decrease in [Cat]0 [3,8].
Scheme III.3.1.
Mn+ + O2 → Mn+...O2 RH→ M(n+1)++ R• + HO2• (1)
ROOH → RO• + •OH (1’)
RH + O2 → R• + • HO2• (1’’)
R• + O2 → RO2•RH→ ROOH + R• (2)
RO2• + M → products + (R’)• (2’)
RH + (R’)• → R• + R’H (2’’)
ROOH +Mn+ → M(n+1)++ OH¯ + RO• RH→ (3)
→ ROOH + R• + M(n+1)+,
ROOH + RO2• → products + (R’)• (4)
ROOH + M(n+1)+ → Mn+ + RO2• + H+, (4’)
2 RO2• → products (5)
RO2• + M → products (5’)

2
k2k2''[RH]
[ROOH]max =
k4 (k2'[M ] + k2''[RH])
k3[M ]
wmax = k22 [RH]2=
2k4k5 (k2[RH] + k2'[M ])
Really, we observed the decrease in the rate of reaction and the growth in [ROOH]max
with the decrease in [Cat]0 (in the case of M(II)(L1)2] ≤ 1,5·10-4 mol/l (M=Ni(II), Co(II))). In
that, the value SPEH,max also increased. We established that in this case, the direction of by-
products formation changed. Products AP and MPC are formed not from PEH but parallel
with PEH, i.e. wP / wPEH ≠ 0 at t→0, and furthermore wAP / wMPC ≠ 0 at t→0, that indicates on
parallelism of formation of AP and MPC (P = AP or MPC) [8].
As mentioned before, the growth in SPEH,max is not accompanied with the increase in the
conversion C. The value C into PEH in the ethylbenzene oxidation, catalyzed by Ni(L1)2
(1,5·10-4 mol/l), was not exceeded C = 2-4% [61,62]. At these conditions, the addition of
electron-donor monodentate ligands turned out to be low effective [8, 25, 29] and the change
of SPEH,max and CS=90% under the introduction of additives L2 (L2 = HMPA, MP) into system,
practically was not observed.
As one can see early, the effective method for increase in parameter C at the conservation
of SPEH,max not less than 90% in the ethylbenzene oxidation, catalyzed by {Ni(L1)2 (1,5·10-4
mol/l) + L2}, is the introduction of activated additives of Ni(II)(acac)2 into developed
reaction.
Coordination of 18C6 or R4NX with Ni(II)(acac)2 seemed to promote oxidative
transformation of nickel (II) complexes (schemes 1–3) into catalytically active particles and
result in increase in C at conservation of SPEH,max not less than 90%. Our assumption was
based on the next literature data.
For example, the ability of crown-ethers to catalyze electrophilic reactions of connection
to γ-C-atom of acac--ligand is known [43, 55].
It is known that R4NX in hydrocarbon mediums forms with acetylacetone complexes
with strong hydrogen bond R4N+(X…HOCMe=CHCOMe)¯ in which acetylacetone is totally
enolyzed [55]. The controlled by R4NX regio-selective connection of O2 by γ-C-atom of
(acac)¯ ligand in complex М(acac)n·R4NX is probable enough. Various electrophilic reactions
in complexes R4N+(X…HOCMe=CHCOMe)¯ proceed by γ-C-atom of acetylacetone [43, 55].
Obviously, the favorable combination of H-bonding and steric factors, appearing under
coordination of 18C6 or R4NX, may not only accelerate the active multi-ligand complex
formation (Schemes 1-4) but also hinder the transformation of active catalyst into inactive
particles.
Our assumption was confirmed. In that, the extraordinary results were received in the
case of the introduction of 18C6 or Me4NBr additives into ethylbenzene oxidation catalyzed
by complexes Ni(L1)2. A really significant increase in conversion degree of oxidation into
PEH at maintenance of selectivity on level SPEH ~ 90% occurs. The degree of conversion into
PEH is increased from 4-6 up to 12% for complexes of Ni(II)(acac)2 (Ni(O,O)2 chelate unit)
with 18C6 (1:1 and 1:2) and from 12 up to 16% for complex of Ni(II)(enamac)2 (Ni(O,NH)2
chelate unit) with 18C6 (1:1); moreover, SPEH exceeded 90%. Furthermore, the addition of
18C6 substantially increases the initial rate w0 of reaction is (Figure 1). The maximum
selectivity of ethylbenzene oxidation SPEH,max increases from 90% to 98-99% [8, 56, 57].
In the case of additives of Me4NBr into reaction of ethylbenzene oxidation catalyzed by
Ni(II)(acac)2, the value of SPEH,max=95% is higher than under catalysis by Ni(II)(acac)2
without addition of L2. The SPEH,max is reached not at the beginning of reaction of
ethylbenzene oxidation, as it occurs at the case of complexes with 18C6, but at C=2-3%.
Selectivity remains in the limits 90% <S≤ 95% to deeper transformation degrees of
ethylbenzene C≈19% than in the presence of additives 18C6 (C≈12%) [8, 95, 96].
Additives of 18C6 or Me4NBr to ethylbenzene oxidation reaction catalyzed by Ni(L1)2
lead to significant hindering of heterolysis of PEH to afford phenol (PhOH). The latter
reaction is responsible for the selectivity reduction in the fully developed process. In that,
induction period of PhOH formation in the presence of Me4NBr additives considerably
exceeded that of the case of 18C6 [56-59].
Influence of quaternary ammonium salt on catalytic activity of Ni(II)(acac)2 as selective
catalyst of ethylbenzene oxidation into PEH extremely depends on the structure of radical R
in ammonium cation. Thus, in the substitution of an n-C16H33 radical for one of methyl
radicals in Me4NBr (if cetyltimethylammonium bromide (CTAB) is added) SPEH,max decrease
from 95 to 80-82% [58,59]. However, the initial reaction rate w0 is significantly increased, in
∼ 4 times in comparison with catalysis of ethylbenzene oxidation by Ni(II)(acac)2 complex.
The initial rate of PEH accumulation wPEH,0 is higher than in the case of ethylbenzene
oxidation catalyzed by the system {Ni(II)(acac)2 + Me4NBr}. However, initial rates of
accumulation of side products of reaction of AP with MPC are also significantly increased
(Figure 3). The decrease in PEH selectivity connected with heterolysis of PEH. The phenol
formation is observed in lower conversions of RH transformation.
Analysis of consequence of ethylbenzene oxidation products’ formation catalyzed by
systems {Ni(L1)2+18C6} and {Ni(II)(acac)2+R4NBr} showed that the mechanism of products
formation is unchanged as compared with oxidations catalyzed by Ni(L1)2 or
{Ni(L1)2+HMPA}. The products PEH, AP and MPC were established to be formed parallel
(wP/wPEH ≠ 0 at t→0) in the course of the process; AP and MPC were formed also parallel
(wAP/wMPC≠0 at t→0).
Ni(O,0)2
Ni(O,NH)2
14 12.64
12 9.65
10 8.61 8.15
wo.10 5
8 6.25 5.38
6 4.44
4 2.36
2 0 0 0 0
0
Figure III.3.1. Dependences of initial rates w0 (mol l-1 s-1) on [18К6] concentration (mol/l) in
ethylbenzene oxidation reactions catalyzed by {M(L1)2+18К6} (M=Ni(II), L1=acac-1, enamac-1).
[M(L1)2]=1,5·10-4 mol/l, 120°С.
Catalysis of ethylbenzene oxidation initiated by {Ni(II)(acac)2 + CTAB} system is not

apparently associated with formation of micro phase such as inverse micelles, because the
micellar effect of CTAB manifested at T < 100° [80] is, as a rule, insignificant at T ≥ 1200.
Furthermore, as we saw the system {Ni(II)(acac)2 + CTAB} was not active in ROOH
decomposition.
For estimation of catalytic activity of nickel complexes as selective catalysts of
ethylbenzene oxidation into α-phenylethylhydroperoxide, we proposed to use parameter S·C.
The S is mean value of selectivity of oxidation into PEH, which evaluated a change of S in the
course of oxidation from S0 at the beginning of reaction to some Slim (Slim is an arbitrary value
chosen as a standard). C − conversion at S = Slim. For comparable by value systems selectivity
as Slim the value Slim = 80%, approximately equal to selectivity of non-catalyzed ethylbenzene
oxidation into PEH at initial stages of reaction, was chosen. The value selectivity was carried
out in the limits S0 ≤ S ≥ Slim (Smax > 80%) (Ni, Co), S0 ≤ S ≤ Slim (Smax = 80%) (Co) [8, 30].
As regards the parameter S·C (S·C ~ 24·102 (%,%)) the system {Ni(II)(acac)2+Me4NBr}
proved to be the most active in ethylbenzene oxidation into PEH as compared with systems
{Ni(II)(L1)2+18C6(HMPA)} [57].
w0 , w.10 6 , mol l -1 s-1

I row-wPEH,0, II-wAP+MPC,0, III-wPEH, IV-wAP+MPC
70
61
60
50
40
27 29 27
30
21 23
19 17
20 16.7 15
11
10
2.6 1.1 2.2 2 1.8 1 2.6 1.3 2.7
000 0
0
Figure III.3.2. Dependences of initial rates w0 (mol l-1 s-1) and the rates w (mol l-1 s-1) in the ethylbenzene
oxidations catalyzed by {M(L1)2+18К6} (M=Ni(II), L1=acac-1, enamac-1) on [R4NBr] (mol/l).
[M(L1)2]=1,5·10-4 mol/l, 120°С.
Methods for Enhancinng the Activityy and Selectiviity… 479
30
24 .3
25 20.6
20
15
9
9.6
10
5
0
2
L =0(HMPPA) 18C6
Me4 NBr
N
Fiigure III.3.3. Paarameter S·C·100-2 (%,%) in thee ethylbenzene oxidation uponn catalysis by caatalytic
syystems {Ni(II)(aacac)2+L2} withh L2=Me4NBr, 18C6,1 HMPА. [Ni(II)(acac)
[ =1.5·10-4 mol/l, 120°C.
2]=
Fiigure III.3.4. Electron absorptiion spectra of aqueous

a solutionns: 1--Ni(acac))2, 2,3, {Ni(acacc)2+18C6},
4,, {Ni(acac)2+MP}, 5, Hacac. [N Ni(acac)2]=1·100-4, [18C6]=2·100-4 (2), 1·10-3 (3), [MP]=1·10-1,
Hacac]=1,9·10-66 mol/l, 200C.
[H
We establiished that in the

t presence of 18C6 or R4NBr alone, without nickeel complex
auuto-catalytic developing
d off process withh initial rates by order, loower was obseerved. The
SPEH
P ,max, equal to 85% (18C6 6) or 95% (MMe4NBr) at the beginning off ethylbenzenee oxidation,
w sharply reeduced with the increase of ethylbenzzene conversiion degree. The
was T PhOH
foormation is ob
bserved from thhe very beginnning of reactioon.
4880 Ludmila
L I. Mattienko, Larisa A. Mosolova and Gennadyy E. Zaikov
-5
Fiigure III.3.5. Abbsorption spectrra of solutions (CHCl
( 3) : 1 – Fe(III)(acac)
F 3 (2,2·10 ), 2 – 6 –
-
-3 -3
{FFe(III)(acac)3+R M 4NBr (2,3·10 ), 3 – ЦТАБ (22,3·10 ), 4 – Bu
R4NBX}: 2 – Me B 4NBr (2,4·10-3), 5 –
-3 -3 0
Bu4NI (2,0·10 ),, 6 – Et3C6H5NC Cl (2,6·10 mol/l), 20 C. (Spectra were recordded using R4NX X solutions
ass a reference).
Synergetic effects of increase in paraameter w0 andd S·C in the ethylbenzene oxidation,

caatalyzed by sy ystems {Ni(L1)2+18C6} andd {Ni(II)(acac)2+R4NBr}, points to the foormation of
acctive complexxes Ni(L1)2 with w (L2) wiith the follow wing composiition 1:1 (L1= (acac)¯,
L2=18C6, R4NB Br), 1:2 (L1= (acac)¯, (enaamac)¯, L2=188C6) and alsoo of their trannsformation
prroducts (Figuure 1(a, b), 2) 2 [98]. The stability of polynuclear heteroligand complexes
1 1 2 1 -
N x(L )y(L ox)z(L )n (L ox= MeCOO
Ni M , L2=18C6,
= R4NB Br) ("А") forrmed in the course of
oxxidation could d be due to thee formation off both inter- annd intra-moleccular hydrogenn bonds. In
thhis case, the foormation of suupramolecular structures is highly
h probablle [62-64].
It was estaablished the influence
i of the
t chelate unnit on the acttivity of bicyyclic nickel
coomplexes Ni(L L1)2 as selectiive catalysts of
o the ethylbeenzene oxidatiion into PEH [8, 30]. In
thhe absence of L2 selectivityy of the ethylbbenzene oxidaation into PEH H not lower thhan SPEH =
800%, increasess considerablyy at catalysis by b Ni(II)(enam mac)2 (Ni(O,N NH)2 chelate unit) up to
C
C=22% as com mpared to thaat for the oxiidation in thee presence of Ni(II)(acac)2 (Ni(O,O)2
chhelate unit) (C ( =11%). The T initial rattes of the oxxidation is thhe presence of o complex
N
Ni(II)(enamac) 2 higher ~ in 2.6 timess (Figure 2).. Besides thi
is, unlike ca
atalysis by
N
Ni(II)(acac) 2 in
n the presence of the compleex with the Nii(O,NH)2 chellate unit, no foormation of
phhenol (the pro oduct of heteroolysis of PEH H) was observed during firsst hours of oxiidation. By
thhe parameter S S·C = 15.9·1002 (%,%), Ni((II)(enamac)2 can be compaared to the Ni(II)(acac)
N 2
coomplexes with 18C6 or Me M 4NBr (Figuure III.3.3, Taable III.3.1). The more effficiency of
N
Ni(II)(enamac) 2 as catalyst as
a compared withw Ni(II)(acaac)2 (w0, S·C) is most likelyy due to the
ellectron-donating NH grouups in the coordination unit of the nickel com mplex. The
trransformation of the catalysst into more acctive selectivee intermediate complexes (thhe increase
in S·C), occurs, in this case, in the absence of additives of activating axial ligand-modifiers L2
(Chap.III.2, Scheme III.2).
The formation of complexes Ni(L1)2 with L2=18C6 or R4NBr was confirmed by UV
spectra. At that, the coordination of ligand L2=18C6 or R4NBr with metal ion proceeds with
preservation of ligand L1 in internal coordination sphere of complex Ni(L1)2 [8, 56-58].
For example, as can be seen from Figure III.3.4, when an aqueous solution of 18C6 is
added to the Ni(acac)2 solution, a decrease in absorption intensity of acetylacetonate ion
(acac)¯ and a short-wave shift of the absorption maximum (spectra 1-3) take place (at that,
ligands 18C6 and MP do not exhibit any absorption bands in region considered). A similar
change in the intensity of the (acac)¯ absorption band is observed in the absorption spectra of
Ni(acac)2 when it is coordinated with monodentate ligand MP (spectrum 4). Evidently, the
formation of a complex between Ni(acac)2 and 18C6 does not lead to displacement of the
acetylacetonate ligand from the inner coordination sphere of Ni(II), because otherwise, the
short-wave shift of the absorption band should be accompanied by a significant increase in
the absorption of the solution at λ = 275 nm, which correspond to the absorption maximum of
acetylacetone (spectrum 5) [56].
Under formation of complexes of Ni(acac)2 with R4NBr, in spite of axial coordination by
the fifth coordination place of nickel (II) ion, the outer sphere coordination of R4NBr (H–
bonding) with acetylacetonate-ion is possible, too.
The possibility of outer sphere coordination of quaternary ammonium salts R4NX with β-
diketonates (Ni(II), Fe(III)) was demonstrated by us with UV spectrophotometry at the
research of the absorption of Fe(III)(acac)3 solutions in the presence of solutions of various
salts R4NX. In the UV edge of the spectrum, Fe complex Fe(III)(acac)3 exhibit an intense
absorption band at ν = 37·103 cm-1 (CHCl3) of the π – π* transition of the conjugated cycle of
the acetylacetonate ion [95, 96]. In the presence of salts R4NX (Me4NBr, CTAB, (C2H5)4NBr,
(C2H5)3C6H5NCl and the other), a decrease in the intensity and a bathochromic shift of the
absorption maximum to ν = 36·103 cm-1 (Δ λ ≈ 10 nm) are observed (Figure 4). Such a
change in the spectrum indicates the influence of R4NX coordinated in the outer sphere on
conjugation in the ligand. The change in the conjugation in the chelate ring of acetylacetonate
complex, when R4NX is coordinated in the outer coordination sphere of the metal, can be
caused by participation of the oxygen atoms of the acetylacetonate ion in the formation of
coordination bonds with the ammonium ion or hydrogen bonds with alkyl substituents of the
ammonium ion [58,596]. For example, it was established that the absorption band of phenol
associated with the π –π* transition experiences a bathochromic shift of 500 cm-1 due to
formation of hydrogen bonds with dioxane[65]
The complexes of the Ni salts with 18C6 and 15C5 (Ni(NO3)2•18C6•6H2O (1),
2NiCl2•15C6•6H2O (2) are more effective catalysts of the ethylbenzene oxidation into PEH in
comparison with systems {Ni(L1)2·18C6n} (S·C = 16.0·10-2 (%,%) (1), S·C = 19.6·10-2 (%,%)
(2)) (Table III.3.1) [57]. In the presence of 1 and 2, the autocatalytic development of the
ethylbenzene oxidation is observed. The transformation of 1 and 2 into the more active
catalytic particles does not occur. Obviously, the presence of the (acac)¯− ligand in the
coordinate sphere of Ni complex is one of the necessary conditions for the high catalytic
activity of complexes Ni(L1)2·18C6n, and also products of their transformation: polynuclear
heteroligand complexes Nix(L1)y(L1ox)z(18C6)n.
Table III.3.1. Parameter S·C in the ethylbenzene oxidation reactions catalyzed by nickel
and cobalt complexes. [Cat]=1.5·10-4 mol/l, 1200C
Cat S·C·10-2(%,%)
Ni(enamac)2 15.9
{Ni(enamac)2+18К6} 21.2
Ni(acac)2 9.6
{Ni(acac)2+18К6} 20.6
Ni(NO3)2·18К6·6H2O(1) 16.0
2NiCl2·15К5·6H2O(2) 19.6
{Co(acac)2+18К62} 9.9
2Co(NO3)2·18К6·6H2O(3) 15.8
2Co(NO3)2·15К6·6H2O(4) 14.1
The higher values of parameter S·C for complex 2 as compared with 1 seems to be due to
the specific feature of binuclear complex NiCl2 with 15C5, and also due to the more stable
bond of Ni – crown-ether for NiCl2, and that may affect on the mechanism of catalysis.
Catalysis by Fe(III)(acac)3 in the Presence of Ligand-modifiers L2
As in the case of ethylbenzene oxidation catalyzed by nickel complexes (Ni(L1)2), at the

catalysis by Fe(III)(acac)3 the SPEH,max increases as [Cat] is reduced. However, this increase is
less significant, from SPEH = 42-46% to SPEH = 65%. We also observed a reduction in the rate
of ethylbenzene oxidation with the decrease of [Fe(III)(acac)3]. However, the dependence of
[PEH]max on [Fe(III)(acac)3] shows an extremum, suggesting that the mechanism of catalysis
is more complicated in this case [38,59, 66].
Fe(III)(acac)3, and formed in the course of ethylbenzene oxidation Fe(II)(acac)2, are
inactive in PEH decomposition [37,58, 65]. In our articles, it was established that in
ethylbenzene oxidation catalyzed by Fe(III)(acac)3 in concentration interval [Cat]=(0.5÷5)·10-
3
mol/l, (80, 120°С) the oxidation products MPC and AP as well as PEH are the major
products. They are formed parallel both at the beginning of reaction and at deeper stages of
oxidation: wP/wPEH and wAP/wMPC is constant and nonzero at t → 0 (P=AP or MPC) [38,59,
66]. The effects of electron-donor exoligands-modifiers on parameters w, SPEH and C of the
ethylbenzene oxidation catalyzed by Fe(III)(acac)3 were studied at [Cat] = 5·10-3 mol/l. In
this case, [PEH] = [PEH]max. In the presence of electron-donor monodentate ligand HMPA
SPEH,max is increased from 42 up to ~57% (80°С), conversion degree C from 5 up to 15%
([Cat] = 5·10-3 mol/l). These were the maximum effects of electron-donor monodentate
ligands on the SPEH and C of ethylbenzene oxidation at catalysis by Fe(III)(acac)3 [38,59]. As
shown above, in the course of oxidation, the Fe(II)−HMPA complexes do not undergo
transformation into more active catalysts of ethylbenzene oxidation to hydroperoxide. After
the acceleration period caused by the formation of Fe(II) complexes via chain initiation by the
Fe(III) complexes (see Chapter VI), which is longer than that in catalysis by Fe(III)(acac)3,
the rate of the reaction under steady-state conditions is w = wmax = wlim (to ~ [PEH]max). The
no additive (synergistic) effects of growth in rate w0 (DMF), wlim (HMPA) and the no
monotonic character of the S·C (see below) dependence on [L2] at [Fe(III)(acac)3] = const
seems to be due to the activity of the resulting Fe(II)(acac)2•L2 complexes, as well as the
complexes produced as a result of the transformation of Fe(II)(acac)2•L2 (L2 is DMF) during
oxidation (Figure III.3.7.).
In ethylbenzene oxidation in the presence of {Fe(III)(acac)3(5·10-3 mol/l)+
R4NBr(0.5·10-3 mol/l)} (R4NBr=CTAB) (80°С), the SPEH,max=65%, which is reached in the
developed process (Figure 9a (1, 2)), is higher than in the case of use of additives of
monodentate ligands HMPA, DMF [38,59]. The fast decrease in SPEH at the beginning steps
of the process is connected with the transformation Fe(III) complexes in Fe(II) complexes in
the course of ethylbenzene oxidation (the auto acceleration period of the reaction is
observed), the increase in wPEH,0, decrease in wP,0, and [PEH]max at catalysis by complexes
(Fe(II)(acac)2)x·(R4NBr)y are observed. Then, the increase in SPEH occurs at the expense of
significant decrease in AP and MPC formation rate in the process at parallel stages of chain
propagation and chain quadratic termination (wP/wPEH ≠ 0 at t → 0, wAP/wMPC ≠ 0 at t → 0).
The conversion degree is increased from C = 4 up to ~ 8% (at SPEH=40-65%) (Figure 9a).
Additives of CTAB to ethylbenzene oxidation reaction catalyzed by Fe(III)(acac)3 lead to
significant hindering of heterolysis of PEH with formation of phenol responsible for decrease
in SPEH.
6 5.46
4.97
5
4 2.9
3 2.1
2
1
0
{Fe(III)(acac)3+Me4N
{Fe(III)(acac)3+CTAB
Fe(III)(acac)3
{Fe(III)(acac)3+(C2H5
)4NBr}
Br}
Figure III.3.6. Parameter S·C·10-2 (%,%) in the ethylbenzene oxidation upon catalysis by Fe(III)(acac)3
and catalytic systems {Fe(III)(acac)3+R4NBr} with R4NBr=Me4NBr, (C2H5)4NBr, CTAB.
[Fe(III)(acac)3]=5·10-3 mol/l, [R4NBr]=0.5·10-3 mol/l, 80°C.
The growth in S·C is ∼ 2.6, 2.36, 1.4 times for R4NBr=CTAB, (С2H5)4NBr), Me4NBr),
respectively, in comparison with catalysis by Fe(III)(acac)3 (S·C=2.1·102 (%,%)) (Figure
III.3.6). In a given case, for value Slim as standard, we accept Slim =40%, a value that
approximately corresponds to the selectivity of ethylbenzene oxidation in the presence of
ligand-free Fe(III)(acac)3 (5·10-3 mol/l) (80°С) under the steady-state reaction conditions, C is
the conversion for which SPEH ≤ Slim. In the absence of a catalyst, the addition of L2 has
practically no effect on selectivity of ethylbenzene oxidation reaction, and the reaction
proceeds in the autocatalytic mode at w0 below that in the catalysis by Fe(III)(acac)3.
The no-additive (synergetic) effects of growth in S·C parameter and w0 observed in the
reactions catalyzed by Fe(III)(acac)3 in the presence of R4NBr, and also obtained kinetic
regularities of ethylbenzene oxidation indicate the formation catalytic active complexes [61]
presumably of (Fe(II)(acac)2)x·(R4NBr)y as well as the complexes, produced as a result of the
transformation of (Fe(II)(acac)2)x·(R4NBr)y during oxidation.
Figure III.3.7. Dependences of selectivity (SPEH) of ethylbenzene oxidation reactions on the conversion
(C) catalyzed by Fe(III)(acac)3 in the absence of additives L2(♦,1) and in the presence of L2= DMF(∆,
2) or L2=HMPA (□, 3) ([DMF]=5·10-2 mol/l, [HMPA]=5·10-2 mol/l). [Fe(III)(acac)3]=5·10-3 mol/l, 1200
C.
The most effect of increase in SC was obtained in the case of CTAB additives. As we
saw at the catalysis by nickel complexes ιν the presence of the CTAB additives, the value of
SPEH,max is reduced down from 90 to 80-82% as compared with increase in SPEH,max (94%) in
the presence of Me4NBr additives [38,59].
Due to the favorable combination of the electronic and steric factors appeared at inner
and outer sphere coordination (hydrogen bonding) of CTAB with Fe(II)(acac)2, the oxidative
degradation of the acetylacetonate ligand may follow “dioxygenase-like” mechanism,
described by Scheme 4. There is a high probability of formation of stable complexes of
structure Fe(II)x(acac)y(OAc)z(CTAB)n (“B”). Out-spherical coordination of CTAB evidently
creates sterical hindrances for regio-selective oxidation of the (acac)¯− ligand and the
transformation of the intermediate complex (“B”) into the final product of dioxygenation.
In the case of catalysis by the {Fe(III)(acac)3 + DMF} system, the complexes
Fe(II)x(acac)y(OAc)z(DMF)n, forming in the process are not stable, though DMF like CTAB
forms H-bonds with acetylacetonate ion [38]. The rapid decrease in SPEH was observed.
SPEH,max at the catalysis by the {Fe(III)(acac)3 + DMF} system was not higher in fact than
SPEH,max at the catalysis by the {Fe(III)(acac)3 in the absence of the additives (Figure III.3.7).
Figure III.3.8. Dependence of SPEH от С in the reactions of the oxidation of ethylbenzene catalyzed by
Fe(III)(acac)3 (♦) or catalytic systems {Fe(III)(acac)3+18C6} (Δ, □). [Fe(III)(acac)3]=5·10-3 mol/l, Δ –
18C6] = 5·10-3 mol/l, □ - 5·10-4 mol/l. 800C.
With the use of HMPA as exo ligand, that did not form H – bonds with chelate ring of
Fe(II)(acac)2, the transformation of Fe(II)(acac)2)·HMPA was not observed, although HMPA
as electron-donor ligand was characterized with a higher DN value (after V. Gutmann) as
compared with DMF (Figure III.3.7) [38].
Catalysis of ethylbenzene oxidation initiated by {Fe(III)(acac)3 + CTAB} system (80°С)
in the case of application of the small concentrations R4NBr (0.5·10-3 mol/l) is not connected
with formation of micro-phase by the type of inverse or sphere micelles. As we saw above,
the system {Fe(III)(acac)3 + CTAB} was not active in decomposition of PEH. wP/wPEH ≠ 0 at
t → 0, wAP/wMPC ≠ 0 at t → 0. Analogous mechanism of formation PEH, AP and MPC is
observed at the use of Me4NBr and (С2H5)4NBr additives, which do not form micelles. At the
[CTAB] concentration [CTAB] = 5·10-3 mol/l the rate of the PEH accumulation and [PEH]max
decreases significantly, since the probability of micelles formation obviously increases.
Thus, we established the interesting fact—the catalytic effect of small concentrations of
quaternary ammonium salts, [R4NBr] = 0.5·10-3 mol/l, which in 10 times less than
[Fe(III)(acac)3]. It is known that salts QX can form complexes with metal compounds of
variable composition, which depends on the nature of solvent [59]. The formation of poly
nuclear heteroligand complexes (Fe(II)(acac)2)x·(R4NBr)y (and Fe(II)x(acac)y(OAc)z(R4NBr)n
also seems to be probable.
In reaction of the oxidation of ethylbenzene with dioxygen, catalyzed by
Fe(III)(acac)3(5·10-3 mol/l) in the presence of 18C6 additives (80°С), the dependence of SPEH
оn С has extremum, as in the case of use of additives of ligands DMF or R4NBr. SPEH,max =
70% ([18C6]0 = 0.5·10-3 mol/l) and SPEH,max = 75.7% ([18К6]0 = 5·10-3 mol/l) in the process
are higher than SPEH,max = 65% in the case of use of CTAB as exo ligand-modifier [57,58,60]
(Figure III.3.8).
The addition of 18C6 in the ethylbenzene oxidation with dioxygen catalyzed by
Fe(III)(acac)3 results in the redistribution of the major oxidation products. The significant
increase in [PEH]max is observed ~ 1.6 or 1.7 times at [18C6] = 5·10-4 mol/l, 5·10-3 mol/l, at
that decrease in [AP] and [MPC] ~ 4, 5 times, accordingly, occurs. Additives of 18C6 lead to
significant hindering of heterolysis of PEH with of the formation of phenol, responsible for
decrease in selectivity.
In the presence of catalytic system {Fe(III)(acac)3+18C6}, synergetic effect of increase in
S·C parameter ~ 2,5 and 2,8 times at [18C6]0=0,5·10-3 mol/l and [18C6]0 = 5·10-3 mol/l,
correspondingly, is observed in comparison with catalysis by Fe(III)(acac)3 (S·C =2,1·102
(%,%)) (Figure III.3.9) [57,58,60].
-2
S·C·10 (%,%)
7
5.89
6 5.3
5
3
2.1
2
0
[18C6]=0; 5.10-4 mol/l; 5.10-3 mol/l
Figure III.3.9. The values of parameter S·C·10-2 (%,%) in the reactions of the oxidation of ethylbenzene
catalyzed by Fe(III)(acac)3 or catalytic systems {Fe(III)(acac)3+18C6}. [Fe(III)(acac)3]=5·10-3 mol/l,
800C.
Obtained kinetic regularities of the oxidation of ethylbenzene testify to formation,

presumably, of (Fe(II)(acac)2)p·(18C6)q complexes and products of their transformations in
the course of oxidation. It is known that Fe(II) and Fe(III) halogens form complexes with
crown-ethers of variable composition (1:1, 1:2, 2:1) and structure dependent on type of
crown-ether and solvent [53].
Supposedly, due to the favorable combination of the electronic and steric factors
appeared at inner and outer sphere coordination (hydrogen bonding) of 18C6 with
Fe(II)(acac)2 (as also in the case of catalysis with complexes with CTAB [96]), there is a high
probability of formation of sufficiently stable hetero ligand complexes of the common
structure Fe(II)x(acac)y(OAc)z(18C6)n, the intermediate products of the oxygenation of (acac)-
ligands in the (Fe(II)(acac)2)p·(18C6)q complexes by analogy to the catalysis by acetyl
acetone dioxygenase (M = Fe(II)) (Dke 1) (Ch. III.2, Scheme 4) that results in the SPEH,max and
C increase:
{Fe(III)(acac)3+18C6}→Fe(II)(acac)p·(18C6)q+O2→Fe(II)x(acac)y(OAc)z(18C6)n (I)
Catalysis by Co(II)(acac)2 in the Presence of Ligand-modifiers L2
As in the case of catalysis of the ethylbenzene oxidation by Ni(L1)2, in the absence of

ligand-modifiers L2 the ethylbenzene oxidation, catalyzed by the relatively low Co(II)(acac)2
concentration (0.5•10-4 mol/l), the selectivity of the catalytic ethylbenzene oxidation into PEH
was sufficiently high: SPEH,max ~ 86%. There was an interesting fact established. The
appearance of PhOH in the oxidation products at the small [Co(II)(acac)2] ≤ 1.0·10-3 mol/l.
The PEH heterolysis with the PhOH formation seems to be due the decrease in Co(II)/Co(III)
ratio with the decrease in catalyst concentration [1,3]. The extreme dependence of SPEH on C
at the small of [Co(II)(acac)2]=(0,5-5)•10-4 mol/l seems to be due the catalyst transformation
in the new catalyst not active in PEH decomposition. In the case of catalysis by Ni(II)(acac)2
at the low catalyst concentration (0.5—1.0)·10-3 mol/l), SPEH,max was observed at the
beginning of the ethylbenzene oxidation. The dependence of SPEH on C has extremum at the
more values [Cat]0 ≥ 1.0·10-2 mol/l [8, 57].
The more significant effect of mono dentate ligand-modifiers L2 not only on SPEH but on
C also was discovered at the increase in [Cat]0. This effect of increase in both parameters SPEH
and C depended from catalyst nature and was established for Ni(II)(acac)2 only. At the
concentrations [Ni(II)(acac)2]0 > 1,5·10-4 mol/l the use of L2 (HMPA) additives results in the
high SPEH,max =80-85% and C = 10-14% of the ethylbenzene oxidation. We established that L2
(HMPA) additives increase SPEH,max but do not change the conversion of the ethylbenzene
oxidation into PEH, catalyzed by Co(II)(acac)2 [94]. In the case of catalysis by Fe complexes,
we observed the increase in C in the presence mono dentate ligand-modifiers L2, at that, the
small effect of increase in SPEH (L2=HMPA) was established or SPEH did not change
practically (L2=DMF) [70].
The additives 18C6 cause significant increase in SPEH,max from 52% (Co(acac)2) up to
80% in the case of {Co(II)(acac)2(1.5·10-4 mol/l)+18C6(3.0·10-4 mol/l)}. But SPEH,max at ratio
[Co(II)(acac)2]/ [18C6]=1:2 ·insignificant exceeds value SPEH,max =72.5% at the catalysis
complexes Co(II)(acac)2•HMPA and nearly coincides with SPEH,max in the ethylbenzene
oxidation catalyzed by coordinated saturated complexes Co(II)(acac)2·2HMPA [33,94]. In
spite of the considerable growth in SPEH,max the catalytic system {Co(II)(acac)2(1.5·10-4 mol/l)
+ 18C6(3.0·10-4 mol/l)} by parameter S·C ( S·C = 9.9·10-2 (%,%) ≈ S·C in the presence of
1,5·10-4 mol/l Ni(II)(acac)2 without additives or in the presence HMPA) is less effective
catalyst of ethylbenzene oxidation into PEH in comparison with {Ni(acac)2+18C6} (Figure
III.3.3). The value w0 is increased in ∼1.6 times at [18К6]:[Co(acac)2]=2:1 ((w0)max) (Figure
III.3.10) [8,57].
Synergetic effects of increase in parameter w0 (the maximum on the dependence w0
against [18C6]) is due to the formation of complexes with different ratio Co(acac)2:18К6 (2:1,
1:1, 1:2) [53,57,30].
As can be seen from Fig III.3.11., at the addition of an aqueous solution of 18C6 to the
Co(II)(acac)2 solution, an increase in absorption intensity of acetylacetonate ion (acac)¯ and a
bathochromic shift of the absorption maximum from ∼ 280 nm (∼35.5·10-3 cm-1) to 290 nm
(∼34.5·10-3 cm-1) take place. The similar changes in the intensity of the (acac)¯ absorption
band and shift of absorption band are characteristic for narrow, crown unseparated ion-pairs
[56]. The formation of a complex between Co(II)(acac)2 and 18C6 occurs at preservation of
ligand L1 in internal coordination sphere of Co(II) because at another case, the short-wave
shift of the absorption band should be accompanied by a significant increase in the absorption
of the solution at λ = 275 nm, which correspond to the absorption maximum of acetylacetone.
Figure III.3.10. Dependence of parameter w0 (•10-4, mol/l) on [18C6] or [HMPA] in the beginning of
the ethylbenzene oxidation (10 min) at the catalysis by {Co(II)(acac)2+18C6} or {Co(II(acac)2 +
HMPA}. [Co(acac)2]=1.5·10-4 mol/l, 1200C. [L2]•104 (mol/l).
Figure III.3.11. Absorption spectra of aqua solutions: of Co(II)(acac)2 (1−−−), mixture {Co(acac)2 +
18C6} (−−−),mixture {Co(acac)2 + МP} (─ • ─•), and Hacac (……). 200C.
Figure III.3.12. Kinetics of PEH (1,2), PhOH (3,4), in the ethylbenzene oxidation, catalyzed by
Co(II)(acac)2, in the absence (1,3) and in the presence (2,4) of 18C6. [Co(acac)2]=1.5·10-4 mol/l,
[18C6]=3.0·10-4 mol/l. 1200C.
Unlike 18C6, the addition of monodentate ligand MP to the Co(II)(acac)2 solution leads
to insignificant decrease in absorption intensity of (acac)¯ ligand and hypsochromic shift of
the absorption maximum (spectrum). The same changes in spectra are observed at the
coordination of Ni(II)(acac)2 with MP (Figure III.3.4), and in the case of the coordination of
axial monodentate ligands with the other metal acetylacetonates [57,70].
At the catalysis by {Co(II)(acac)2+18C6} system, the kinetic curves of the ethylbenzene
oxidation products have characteristic inflections apparently caused by formation of
complexes providing higher selectivity of ethylbenzene oxidation into PEH (Figure III.3.12,
III.3.13) [8, 57]. In the presence of Co(II)(acac)2 and additives of 18C6 (or HMPA), the rate
of accumulation of the products is maximum at the early stages of the reaction and passes
through a minimum as the degree of oxidation increases.
As mentioned above, the formation of active selective catalyst in the ethylbenzene
oxidation, catalyzed by system {Co(II)(acac)2 + HMPA}, likely, did not follow the
mechanism of the oxidation of (acac)¯ ligand with the molecular oxygen. The analogy of
ethylbenzene oxidation phenomena in these two cases of catalysis by {Co(II)(acac)2+18C6}
and {Co(II(acac)2 + HMPA} seems to be due similar mechanism of catalyst transformation
(see Chapter III.2). The Co(II) Co(III) transition under the action of peroxide radicals
seems to be the most probable.
The effects of increase in SPEH,max accompanied by decreases in rates of AP and MPC
formation, are observed also at the catalysis by complex of Co(NO3)2 with 18C6
(2Co(NO3)2•18C6•6H2O) in the absence of (acac)¯− ligand [94]. This fact probably testifies in
favor the interaction of Co(II)(L1)2·18К62 with RO2• radicals with the formation of active
selective catalyst of structure [Co(III)(L1)2·18К62·(RO2⎯)]. The similar complexes were
assumed at the research of cumyl ROOH decomposition in the presence of adducts
Co(II)(acac)2·Py (L1=acac-, L2=Py (Py=pyridine)) [8,67,68]. The formation of Co(II)(acac)2
complexes with peroxide radicals in the {Co(II)(acac)2+ROOH} system was not registered.
As one can see before the Co(II)(acac)2 transformation, as a result of (acac)¯ ligand, oxidation
[7,57] evidently takes place in the course of the ethylbenzene oxidation, catalyzed with
Co(II)(acac)2 in the absence of ligand - modifier L2.
Figure III.3.13. Kinetics of AP (1,2), MPC (3,4) in the ethylbenzene oxidation, catalyzed by
Co(II)(acac)2, in the absence (1,3) and in the presence (2,4) of 18C6. [Co(acac)2]=1.5·10-4 mol/l,
[18C6]=3.0·10-4 mol/l. 1200C.
At the coordination 18C6 (HMPA) with Co(II)(acac)2 (1.5•10-4 mol/l), the sequence of
products formation of the ethylbenzene oxidation is unchanged. The products PEH, AP and
MPC were established to be formed parallel (wP/wPEH ≠ 0 at t→0), AP and MPC – also
parallel (wAP/wMPC≠0 at t→0) throughout the reaction of ethylbenzene oxidation.
Analogy tendency for the ratio of the rates of accumulation of products PEH, AP and
MPC to change for reaction time t→0 was observed at the catalysis by complex of Co(II) salt
Co(NO3)2 with 18C6 (2Co(NO3)2•18C6•6H2O (3)) (Table III.3.1). The transformation of the
Co(II) salts with crown-ethers depends on the nature of crown-ether and does not occur with
complex 2Co(NO3)2•15C5•6H2O (4). By parameter S·C the complexes of the Co(II) salts with
18C6 or 15C5 (3), (4) are more effective catalysts of the ethylbenzene oxidation into PEH in
comparison with system {Co(acac)2·18C62} (S·C = 15.8·10-2 (%,%) (3), S·C = 14.3·10-2
(%,%) (4) [33,93]) unlike the tendency, established by us for complexes of the Ni salts with
18C6.
The transformation of the Co(II) salts 3 (Co-18К6) occurs in the absence of ligand L1
(L1=(acac)-), and seems to be due to a result of interaction of 3 with RO2• radicals with the
formation of active selective catalyst (Scheme III.3.2).
Scheme III.3.2.
III.4. TRIPLE CATALYTIC SYSTEMS INCLUDING BIS

(ACETYLACETONATE) NI(II) AND ADDITIVES OF ELECTRON-DONOR
COMPOUND L2 AND PHENOL AS EXO LIGANDS
One of the most effective methods of control of selective ethylbenzene oxidation into α-
phenylethylhydroperoxide with dioxygen may be the application of the third component of
the catalytic system, phenol (PhOH), along with Ni(II)(acac)2 and the additives of electron-
donor ligands L2 (L2= MSt (M=Na, Li), MP, HMPA) [69].
Previously, we established that in the reaction of the ethylbenzene oxidation, catalyzed by
Ni(II)(acac)2 in the absence of ligand-modifiers L2 the sharp decrease of rate and selectivity at
the initial stages of oxidation is connected with formation of complex Ni(II)(acac)2·PhOH
that was an effective inhibitor of the ethylbenzene oxidation: under the action of
Ni(II)(acac)2·PhOH, heterolytic decomposition of PEH into PhOH and acetaldehyde took
place, and also Ni(II)(acac)2·PhOH terminated the chains of oxidation reacting with RO2• -
radicals [3,5-6].
We discovered phenomenon of the considerable increase in the efficiency of selective
ethylbenzene oxidation reaction into α-phenylethylhydroperoxide with dioxygen in the
presence of triple systems {Ni(II)(acac)2+L2+PhOH} (L2=MP, HMPA MSt (M=Na, Li)),
parameters S·C, the conversion degree C (at SPEH ~85 to 90%), and the hydroperoxide
contents ([PEH]max), in comparison with catalysis by binary systems {Ni(II)(acac)2+L2}. In
this case. the value of SPEH is high (about 85 to 90%) both at the beginning of the reaction and
at the significant depth of the process, unlike the catalysis by {Ni(II)(acac)2 + L2}. In the
latter case, as one can see higher, the dependence of SPEH on C has a well-defined extremum.
For example, at the catalysis by {Ni(II)(acac)2 + MP} SPEHmax =85 to 87% at C ~ 8 to 10%
(Figure III.4.1).
Figure III.4.1. Dependence of SPEH on C in reaction of ethylbenzene oxidation catalyzed by binary

system {Ni(II)(acac)2+МP} (♦, 1) and two triple systems {Ni(II)(acac)2+МP+ PhOH} with [PhOH]=
3·10-3 mol/l (□, 2) or 4.6·10-4 mol/l (Δ, 3) and [Ni(II)(acac)2] = const = 3·10-3 mol/l, and [МP] = const
= 7·10-2 mol/l. 1200C.
As is evident, phenomenal results were obtained in the case of application of system,

including NaSt as L2 {Ni(II)(acac)2 (3.0·10-3 mol/l) + NaSt (3.0·10-3 mol/l) + PhOH (3.0·10-
3
mol/l)} (Table III.4.1). Parameter C > 35% at the SPEHmax =85-87%. Concentration
[PEH]max = 1.6 -1.8 mol/l (∼27 mass %), that is higher than [PEH]max for all binary catalytic
systems {Ni(II)(acac)2 + L2} studied by us earlier and also the most effective triple catalytic
systems {Ni(II)(acac)2 + L2 + PhOH}. Parameter S·C ∼ 30.1·102 (%,%) is much higher than
in the case of the other triple systems and the most active binary systems [33]. These data are
protected by patent RU No.2237050. Registration date is 11.2.2004; the authors are L.I.
Matienko and L.A. Mosolova; patent holder is Emanuel Institute of Biochemical Physics,
Russian Academy of Sciences.
Table III.4.1.
[МP], mol/l S·C·10-2(%,%)

0 0
0.3·10-2 0.29
3.0·10-2 11.30
7.0·10-2 17.50
21.0·10-2 11.20
20.0·10-2* 11.00
Table III.4.2.
[Ni(II)(acac)2], mol/l S·C·10-2 (%,%)

1.0·10-3 15.41
3.0·10-3 17.47
5.0·10-3 12.65
Figure III.4.2. Dependence of parameter S·C·10-2(%,%) on [PhOH] in reaction of ethylbenzene

oxidation catalyzed by {Ni(II)(acac)2+MP+PhOH}. [Ni(II)(acac)2] = const = 3·10-3 mol/l, [MP] = const
= 7·10-2 mol/l. 120°C.
Mechanism of selective ethylbenzene oxidation into α-phenylethylhydroperoxide in the

presence of triple systems is demonstrated here on the example of {Ni(II)(acac)2 + MP +
PhOH} system. While investigating dependence of parameter S·C on [МP] in oxidation
reaction in the presence of {Ni(II)(acac)2 + MP + PhOH} at [Ni(II)(acac)2]=const=3·10-3
mol/l and [PhOH]=const=3·10-3 mol/l (120°С), it turned out that dependence is extreme
(Table III.4.1.).
Maximum value of S·C is reached at [MP] = 7·10-2 mol/l (Smax=85-87%). Concentration
[MP] = 7·10-2 mol/l corresponds to formation of complexes of Ni(II)(acac)2 with MP of
structure 1:1 (in the absence of PhOH) [8, 69]. It is characteristic that the value (S·C)max
=17.5·102 (%,%) exceeds value S·C for complexes Ni(II)(acac)2·MP (11.9·102 (%,%)) and
coordinated saturated complexes Ni(II)(acac)2·2MP. Observing the significant synergetic
effect of parameter S·C increase under catalysis by {Ni(II)(acac)2 + L2} in the presence of
inhibitor phenol may be explained by unusual catalytic activity of formed triple complexes
Ni(II)(acac)2·(L2)·(PhOH). This presumption is confirmed by dependences of S·C on
[Ni(II)(acac)2] at [PhOH]=const=3·10-3 mol/l and [МP]=const=7·10-2 mol/l
((S·C)max=17.47·102 (%,%) at [Ni(II)(acac)2]=3·10-3 mol·l-1) (Table III.4.2.), and also of S·C
on [PhOH] at [Ni(II)(acac)2]=const=3·10-3 mol/l and [МP]=const=7·10-2 mol/l. In the latter
case, S·C reaches the extremum (S·C)max=17.5 and (S·C)max =18.12·102 (%,%) at two
[PhOH] concentrations differing by an order of magnitude: [PhOH] = 3·10-3 and 4.6·10-4
mol/l accordingly (Figure III.4.1, III.4.2). The data, presented in Figure III.4.1, III.4.2, testify
to the fact that in both of these cases, selective ethylbenzene oxidation into PEH is connected
with formation of the catalytic active complexes with composition 1:1:1. The confirmation of
these triple complexes formation in the process came from the comparison of kinetics of the
products accumulation of the ethylbenzene oxidation catalyzed by two triple systems
{Ni(II)(acac)2(3·10-3 mol/l) + МP(7·10-2 mol/l) + PhOH} at [PhOH] = 3·10-3 or [PhOH] =
4.6·10-4 mol/l. Some differences observed at the initial stages of two reactions are caused by
the different initial conditions of triple complexes Ni(II)(acac)2·(L2)·(PhOH) formation in the
course of catalytic ethylbenzene oxidation in these cases.
At catalysis by triple system {Ni(II)(acac)2+МP+PhOH} with small [PhOH]=4.6·10-4
mol/l, the fast increase in the concentration of PhOH right up to [PhOH] = (3-5)·10-3 mol/l
(at t=0-5 h) is observed. [PhOH] = (3-5)·10-3 mol/l ∼ corresponds to [PhOH] for the first
combination {Ni(II)(acac)2 (3.0·10-3 mol/l) + МP (7.0·10-2 mol/l) + PhOH (3.0·10-3 mol/l)}
and to the formation of complexes of structure [М(L1)2·(L2)·(PhOH)] (Figure III.4.3 (2)).
The increase in the concentration of PhOH (a result of PEH heterolysis) at the beginning
of the process may be due to the function of PhOH as an acid that became stronger in
consequence of outer sphere coordination of PhOH with nickel complex Ni(II)(acac)2·МP
[61]. This presumption is confirmed by the next facts. So the accumulation of PhOH, but not
the consumption, with maximum initial rate wPhOH,0=wPhOH,max is observed upon addition of
PhOH (3.0·10-3 mol/l) into the reaction of ethylbenzene oxidation catalyzed by coordinated
saturated complexes Ni(II)(acac)2·2MP ([Ni(II)(acac)2] = 3.0·10-3 mol/l, [МP] = 2.1·10-1
mol/l) (Figure III.4.4), and also in the case of the ethylbenzene oxidation catalyzed by binary
system {Ni(II)(acac)2(3.0·10-3 mol/l) + PhOH(4.6·10-4 mol/l)} at [МP] = 0 [69].
Figure III.4.3. Kinetics of accumulation of PhOH in reaction of ethylbenzene oxidation catalyzed by

binary system {Ni(II)(acac)2+МP} (1) and two triple systems {Ni(II)(acac)2 + МP + PhOH} with
variable values of [PhOH] = 4.6·10-4 mol/l (2) or 3·10-3 mol/l (3) and [Ni(II)(acac)2] = const = 3·10-3
mol/l, and [МP] = const = 7·10-2 mol/l. 1200C.
Figure III.4.4. The dependences of SPEH (◊) and [PhOH] (□) от C in reaction of ethylbenzene oxidation
in the presence of triple system {Ni(II)(acac)2 (3,0·10-3 mol/l)+МП(2,1·10-1 mol/l)+PhOH (3,0·10-3
mol/l)}, 1200C.
The consumption of PhOH at the beginning of the process in the presence of catalytic
system {Ni(II)(acac)2 (3.0·10-3 mol/l) + MP (7.0·10-2 mol/l) + PhOH (3.0·10-3 mol/l)}with
[PhOH] = 3·10-3 mol/l (Fig III.4.3 (3)) may be due to the formation of the triple complexes
[М(L1)2·(L2)·(PhOH)] and least of all due to consumption of PhOH as inhibitor in the
reaction of chain termination, PhOH + RO2•→. The rate of PhOH consumption is actually
unchanged in a wide interval of MP concentration (0.3÷7.0)•10-2 mol/l. Previously, it was
established that the rate of RO2• formation in the ethylbenzene oxidation catalyzed by
Ni(II)(acac)2 (3.0·10-3 mol/l) at the addition of MP increased significantly due to the increase
in the activity of the formed complexes Ni(II)(acac)2·MP in the reaction of chain initiation
and homolytic decomposition of PEH [8, 26].
Similarity of phenomenology of the ethylbenzene oxidation in the presence of
{Ni(II)(acac)2 (3.0·10-3 mol/l) + MP (7.0·10-2 mol/l) + PhOH (3.0·10-3 mol/l)} and
{Ni(II)(acac)2 (3.0·10-3 mol/l) + NaSt (LiSt) (3.0·10-3 mol/l) + PhOH (3.0·10-3 mol/l)}
allows assuming the analogous mechanism of selective catalysis realizing by triple complexes
formed in the course of oxidations. Also, the parallel formation of PEH and side products AP
and MPC is established in these two cases: wP/wPEH ≠ 0 at t→0 (P=AP or MPC) and
wAP/wMPC≠0 at t→0 at the beginning of reaction and in developed reaction of ethylbenzene
oxidation catalyzed by {Ni(II)(acac)2+L2+ PhOH} (L2 = NaSt (LiSt), MP). Increase in SPEH
during the catalysis by complexes Ni(II)(acac)2·L2·PhOH (L2 = NaSt, MP) in comparison
with non-catalyzed oxidation is connected with the change of direction of the formation of
side products AP and MPC (AP and MPC are not formed from PEH, as it takes place in non-
catalyzed oxidation) and also with hindering of heterolytic decomposition of PEH [69].
Interesting phenomenon was established. Depending on the ligand surrounding of nickel
ion, the PhOH becomes both effective as a deactivating ligand and as an effective activating
ligand. In the absence of the exo ligand L2, the coordination of PhOH to Ni(II)(acac)2
(complex 1:1) is favorable to heterolytic decomposition of PEH and inhibition of the
ethylbenzene oxidation [3, 5-6]. In the presence of the exo ligand L2, the formed triple
Ni(II)(acac)2·L2·PhOH complexes, that include PhOH, are the effective catalysts of the
selective ethylbenzene oxidation to α-phenylethylhydroperoxide with molecular O2.
The advantage of these triple systems is a long-term activity of in situ formed complexes
Ni(II)(acac)2·L2·PhOH, which are not transformed in the course of ethylbenzene oxidation.
Apparently, the introduction of phenol, together with the {Ni(II)(acac)2 + L2} catalyst in
the reaction system in the initial stage of ethylbenzene oxidation, is one of the most
efficient methods of designing catalytic systems for the ethylbenzene oxidation
to α-phenylethylhydroperoxide. The high efficiency of three-component systems
{Ni(II)(acac)2+MSt+ PhOH} (M= Na, Li) in the reaction of selective ethylbenzene oxidation
to α-phenylethylhydroperoxide was associated with the formation of extremely stable
heteroligand complexes Ni(II)(acac)2·MSt·PhOH, which resulted in considerable increase in
the conversion of ethylbenzene to PEH and the yield of α-phenylethylhydroperoxide.
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INDEX
additives, xv, 21, 76, 365, 368, 383, 392, 492, 521,
A 522, 533, 534, 538, 539, 544, 546, 548, 549, 550,
551, 552, 554, 556
absorption, 534, 542, 544, 552, 554
adducts, 535, 555
absorption spectra, 542, 544
adenocarcinoma, 509
academic aspects, x, 47
adhesives, 401
acceleration, 526, 546
adsorption, 26, 198, 274, 446
acceptor, 534
aerogels, 7, 198, 207
acceptors, 534
AFM, 191, 192
accessibility, 26, 280, 282, 288, 385, 461, 523
agencies, 213
accounting, 83, 283
aggregation, 25, 26, 174, 178, 189, 206
acetaldehyde, 19, 498, 527, 530, 556
agriculture, 437
acetic acid, 12, 20, 234
air, 523
acetone, 9, 16, 24, 25, 183, 193, 288, 421, 525, 530,
alcohols, xiii, xv, xvi, 7, 8, 18, 20, 29, 49, 62, 65, 70,
551
74, 76, 80, 149, 187, 200, 209, 228, 234, 235,
acetonitrile, 80, 159, 179, 267, 271, 383, 423, 428,
247, 253, 254, 261, 310, 316, 324, 325, 327, 332,
429
344, 387, 417, 418, 424, 425, 426, 437, 440, 442,
acetophenone, 9, 25, 300, 304, 305, 376, 469, 524,
444, 452, 497, 498, 501, 522
525, 526, 531
aldehydes, xiv, xv, xvi, 18, 26, 48, 49, 83, 179, 180,
acetylation, 437, 440, 442, 445, 451, 452
184, 185, 206, 215, 218, 223, 234, 235, 237, 259,
acidic, 526
280, 309, 310, 317, 321, 323, 324, 326, 327, 329,
acidity, 160
330, 368, 417, 418, 425, 465, 498, 504, 505
acrylate, 147, 217, 219, 220, 221, 222, 396, 470,
algorithm, 165
471, 472, 474
aliphatic amines, 251, 262, 497
acrylic acid, 11, 21, 234, 291, 303
alkaloids, xv, 25, 252, 262, 366, 368, 396
acrylonitrile, x, 48, 288
alkanes, 522, 523
activated carbon, 11, 19, 30
alkenes, xiii, 10, 18, 19, 31, 49, 69, 145, 220, 233,
activation, 522, 524, 525, 526, 532, 533, 534
339, 342, 353, 354, 355, 368, 387, 389, 400, 402,
activation energy, 51, 374
470
activation parameters, 51
alkoxycarbonylation, xiii, 233, 235, 247, 252, 253,
active centers, xi, 26, 108, 110, 115, 117, 118, 122,
254, 262, 263
123, 124, 125, 128, 129, 134, 136, 138, 139
alkylarens, 526
active oxygen, 399
alkylation, xii, 54, 144, 187, 188, 320, 324, 331, 348,
active site, x, 7, 47, 48, 113, 118, 122, 138, 139, 150,
349, 368, 373, 374, 377, 381, 382, 383, 394, 406,
177, 281, 283, 336, 378, 380, 407, 523, 524, 536
408, 501
acylation, 237, 437, 440, 441, 444, 450, 451, 505
alkylation reactions, 373, 408
adamantane, 152
AlR3, 115, 139
adaptation, 267
aluminium, x, 4, 107, 109, 112, 115, 118, 122, 124,
136, 138
aluminum, 523
500 Index
amides, xiii, 18, 62, 74, 204, 233, 235, 246, 247, basic raw materials, 234
251, 262, 489, 490, 494 basicity, 159, 160, 163, 183, 206
amine, 13, 23, 49, 183, 185, 246, 250, 284, 285, 311, behaviors, 217
316, 321, 337, 388, 392, 472, 487, 492, 496, 501 Beijing, 435
amino acid, 248, 249, 250, 258 bending, 446
aminocarbonylation, xiii, 233, 235, 246, 247, 248, benefits, 2, 266
249, 250, 251, 262, 263 benign, xv, 211, 212, 234, 251, 365, 366, 367, 371,
ammonia, 11, 24, 243, 260, 494, 501 372, 485
ammonium salts, 15, 377, 384, 399, 535, 536, 544, benzene, 7, 8, 14, 20, 24, 25, 28, 148, 153, 166, 271,
549 282, 303, 306, 347, 378, 420
amorphous polymers, 177 binding energies, 164
analgesic, 383 binuclear, 534, 536, 545
anatase, 3 biocatalysis, 532
anchoring, 7 biocatalysts, 228
aniline, 12, 23, 30, 249 biochemistry, 266
anticancer studies, xvii, 456, 509 biodegradability, 212
anticonvulsant, 261 biodiesel, 212, 213, 222
antidepressant, 146 bioenergy, 436
antipyretic, 383 biofuel, 212
application, xvii, 521, 549, 556, 557 biological activity, 392
aqueous solution, 535, 542, 544, 552 biological systems, x, 48
aqueous suspension, 25 biologically active compounds, 61, 241, 258
ARCO and Halcon processes, x, 48 biomass, 436, 449
arc-plasma method, 5 biomaterials, 176, 205
argon, 5, 390 biomedical applications, xvii, 456, 457, 469, 509
aromatic compounds, 535 biopolymers, 436
aromatic rings, 14, 150, 187 bioremediation, 532
aromatics, 213 bis, x, xi, xiv, 8, 10, 17, 20, 63, 66, 107, 108, 109,
ascorbic acid, 23 110, 112, 113, 114, 115, 116, 118, 120, 122, 124,
Aspergillus terreus, 216 125, 128, 129, 130, 134, 137, 138, 139, 140, 146,
asymmetric chemistry, xi, 143 155, 156, 166, 167, 216, 223, 239, 242, 263, 265,
asymmetric hydrogenation, ix, xi, xii, 25, 144, 148, 267, 294, 298, 348, 351, 390, 464, 466, 467, 469,
165, 166, 291, 294, 296, 297, 298, 299, 302, 303, 470, 471, 483, 490, 497, 499, 502, 524, 525
305, 306, 307, 308 BMI, 10, 16, 20
asymmetric synthesis, xiv, 145, 158, 166, 280, 281, bonding, 174, 198, 205, 529, 539, 544, 548, 551
357, 504 bonds, xvii, 8, 14, 116, 174, 189, 257, 316, 320, 355,
asymmetry, xv, 316, 366, 368 386, 429, 436, 455, 456, 457, 462, 525, 527, 532,
atmosphere, 54, 200, 235, 256, 438, 439 535, 536, 543, 545, 549
atmospheric pressure, 26, 243, 251, 254, 262, 291 branching, 29, 76, 137, 280, 283, 313
atoms, 29, 51, 52, 77, 78, 79, 81, 83, 113, 146, 149, Brazil, 37, 265
150, 153, 154, 157, 159, 161, 234, 290, 312, 314, breakdown, 529, 532
350, 421, 430, 485, 524, 525, 545 breast cancer, 509
attachment, 197, 280, 294, 356 Bruker DRX, 440
Au nanoparticles, 29 BTC, 199, 200
auto acceleration, 546 building blocks, 48, 257, 436
automation, 266 butadiene, 8, 20, 61, 501
automatization, 163 Butcher, 101, 519
awareness, 82 by-products, 210, 219, 538
B C
Baars, 415 cancer cells, 508

bacteria, 536 capillary, 269
barriers, 7, 26 carbohydrate, 151, 448
Index 501
carbohydrates, 28 chain termination, 537, 560

carbon atoms, 83, 273, 399, 402, 420, 421, 448, 524 chain transfer, 118, 124, 125
carbon dioxide, xiii, 7, 209, 212, 228 chemical, ix, x, xi, xii, xvi, xvii, 4, 5, 13, 17, 20, 24,
carbon materials, 9 25, 30, 47, 48, 49, 61, 143, 163, 174, 176, 178,
carbon monoxide, xi, xiii, 11, 108, 110, 116, 233, 209, 210, 211, 212, 213, 214, 234, 247, 266, 273,
234, 235, 236, 238, 241, 242, 243, 244, 246, 248, 280, 285, 287, 307, 316, 321, 328, 329, 337, 356,
250, 252, 254, 257, 260, 261, 309 366, 367, 371, 372, 379, 403, 417, 436, 437, 444,
Carbon monoxide, xiii, 233, 532 450, 451, 456, 509, 523, 532
carbon nanotubes, 3, 7, 11 chemical industry, 234, 266
carbonyl groups, 441, 444, 446 chemical inertness, 307
carbonylation, xiii, 233, 234, 235, 236, 237, 238, chemical properties, xii, 209, 211, 214, 280, 287
239, 241, 242, 244, 247, 248, 252, 253, 254, 255, chemical reactions, ix, x, 47, 48, 366, 372
256, 257, 258, 259, 260, 261, 262, 263, 352, 457 chemical structures, 356
carbonylative, ix, xiii, 234, 235, 237, 238, 239, 240, chemicals, 49, 227, 234, 235, 383, 438, 489
241, 242, 243, 244, 245, 246, 251, 256, 257, 258, China, 173, 202, 365, 435, 438, 449
259, 260, 261, 262, 263, 314 chiral catalyst, 62, 165, 319, 324, 327, 328, 329, 330,
carbonylative Sonogashira coupling reaction, xiii, 346, 368
234, 242, 244, 246, 261 chiral center, 83
carboxyl, 446 chiral molecules, xv, 366, 368
carboxylic acid, xiii, 11, 15, 224, 233, 234, 235, 247, chiral product, xi, xii, 143, 144
254, 259, 262, 387, 422 chirality, 66, 83, 145, 147, 152
carboxylic acids, xiii, 224, 233, 235, 254, 259, 262, chitin, 23
387, 422 chitosan, 23
carrier, 523 chlorine, 9, 452
castor oil, 203 chlorobenzene, 17, 282, 377, 487
catalyst deactivation, xviii, 357, 426, 521 chloroform, 28, 88, 288, 327, 377, 400, 401
catalytic activity, xiv, 2, 3, 5, 8, 16, 24, 25, 26, 31, chromatograms, 269
56, 63, 73, 87, 88, 90, 92, 109, 118, 130, 183, chromatography, xiv, 265, 285, 319, 327, 338, 339,
184, 189, 197, 198, 266, 267, 274, 276, 290, 291, 419
293, 300, 302, 304, 311, 316, 320, 328, 340, 342, chromium, 3, 108, 109, 130, 134, 137, 139, 140, 421,
344, 350, 351, 353, 354, 377, 378, 407, 428, 468, 422
471, 473, 524, 526,뫰535, 536, 539, 540, 545, Cinchona alkaloids, xv, 366, 368
cis, 525
558
City, 32
catalytic effect, 3, 437, 549
clarity, 52
catalytic hydrogenation, 8, 14, 19, 27, 145, 223, 227,
classes, 160, 286, 369, 468
228, 287, 294, 428
cleaner processes, ix, 47
catalytic particles, xvii, 521, 545
cleavage, 13, 79, 202, 522, 528, 532
catalytic properties, xi, xii, 10, 54, 61, 93, 108, 109,
clinical trials, 266
110, 139, 173, 202, 282, 294, 298, 302, 311, 327,
closure, 392
426
clusters, 26, 29, 426
catalytic step, ix, 47
CNS, 247
cation, 243, 339, 374, 384, 399, 400, 402, 426, 539
CO2, 9, 15, 22, 24, 25, 26, 93, 212, 525
cavities, 536
cobalt, 7, 108, 109, 120, 121, 122, 123, 124, 125,
C-C, xiv, 19, 194, 220, 226, 280, 429, 510, 532
128, 130, 139, 140, 310, 420, 545
cell cycle, 509
cocatalyst, 397, 399, 400, 401, 488, 498
cell line, 509
coenzyme, 536
cellulose derivatives, 437, 441, 442, 444, 445, 448,
collagen, 3
449
colon, 509
cellulose succinoylation, xvi, 435, 437, 440, 441,
color, 183, 439
442, 447, 449
combustion, 8
cervical cancer, 509
commodity, 235
cesium, 13
community, 69, 96, 372, 394
chain propagation, 117, 118, 527, 537, 547
502 Index
compatibility, 242, 247, 389, 536 coupling constants, 159

competitive process, 381 covalent bond, 153, 174, 178
compilation, ix, 1 creativity, 147, 408
complement, 157 critical analysis, xv, 366, 371
complexity, xii, 144, 160, 161, 202 crown, 27, 383, 394, 402, 403, 404, 467, 536, 538,
composites, 3, 7, 18, 20, 27, 31, 449, 450 545, 551, 552, 555
composition, xi, 4, 53, 108, 109, 110, 116, 118, 120, crystal structure, 92, 175, 251, 349
121, 122, 138, 210, 285, 527, 543, 550, 551, 559 crystalline, 7, 9, 28, 155, 175, 176, 269, 288, 436,
compounds, ix, xiii, xv, xvi, xvii, 5, 9, 25, 31, 47, 50, 448, 525
52, 53, 54, 56, 61, 65, 69, 74, 83, 92, 145, 163, crystallites, 6
179, 203, 209, 211, 213, 214, 216, 218, 223, 227, crystallization, 280
228, 234, 235, 238, 245, 246, 248, 256, 258, 259, crystals, 177, 202, 424
261, 262, 266, 269, 270, 298, 310, 321, 342, 366, CS, 534, 538
386, 387, 389, 392, 399, 403, 417, 419, 421, 422, CTAB, 535, 539, 540, 544, 546, 547, 548, 549, 550,
425, 427, 429, 430, 436, 456, 503, 505, 509, 521, 551
522, 528, 535, 536, 550 cyanide, 367
computational chemistry, xii, 144 cycles, xvii, 156, 161, 243, 303, 351, 456, 457, 460,
computing, 158, 165, 285 488
concentration, 532, 533, 537, 541, 546, 549, 551, cyclodextrins, 10, 26
559, 560 cyclohexane, 523
condensation, xvi, 5, 8, 27, 91, 215, 222, 223, 261, cyclohexanol, 8, 14, 523
320, 347, 418 cyclohexanone, 8, 14, 185, 374, 375, 376, 523
conductivity, 212 cyclohexyl, 523
configuration, 65, 157, 161, 164, 390, 402, 418, 527, cyclopentadiene, 291
529 cytotoxicity, 509
conjugated dienes, 291, 421 Czech Republic, 143, 166, 417
conjugation, 380, 544
conservation, 538
D
construction, xiv, 164, 178, 279, 283, 290, 456, 461,
deacetylation, 65
485, 502
decay, 525
consumption, 373, 559, 560
decomposition, 5, 7, 10, 17, 22, 26, 51, 53, 54, 57,
contaminant, 31
79, 93, 210, 211, 221, 350, 357, 492, 499, 522,
contamination, 210
526, 528, 530, 535, 537, 540, 546, 549, 551, 555,
contradiction, 174
556, 560, 561
control, xvii, 521, 523, 526, 556
decomposition reactions, 54
conversion, 522, 526, 530, 532, 533, 534, 538, 539,
decomposition temperature, 53
540, 543, 546, 547, 548, 551, 556, 561
defects, 284, 286
cooling, 179, 197, 267, 439
deformation, 174, 177
coordination, x, xi, xii, 5, 48, 51, 57, 65, 73, 74, 76,
degradation, 23, 426, 523, 548
77, 80, 92, 136, 144, 146, 154, 173, 174, 178,
dendrimers, xiv, 2, 20, 26, 29, 213, 279, 280, 281,
192, 193, 195, 197, 198, 200, 202, 204, 206, 207,
282, 283, 284, 285, 286, 287, 288, 290, 291, 292,
222, 269, 312, 323, 332, 419, 485, 488, 496, 526,
294, 298, 300, 302, 310, 311, 312, 314, 315, 316,
527, 529, 539, 544, 548, 551, 552, 554, 555, 559,
317, 319, 324, 325, 326, 328, 329, 331, 332, 334,
561
335, 339, 345, 349, 350, 351, 353, 354, 356, 357,
copolymer, 6, 16, 22, 28, 224
359
copolymers, 406, 453, 525
Denmark, 510, 517
copper, ix, 1, 3, 7, 49, 197, 207, 246, 488, 524
density functional theory, 166
correlation, 18, 20, 155, 159, 160, 164, 203, 204
Department of Energy, 436
corrosion, 3
deposition, 3, 4, 23, 27, 31
cosmetics, 212, 213
derivatives, xiii, xvi, 9, 15, 26, 52, 53, 54, 57, 62, 66,
cost, xv, 29, 213, 347, 365, 367, 463, 485
82, 83, 84, 88, 92, 93, 96, 148, 151, 182, 191,
cotton, 452
204, 212, 213, 233, 234, 235, 238, 245, 247, 248,
coumarins, 255, 256, 263
253, 254, 258, 261, 262, 263, 308, 316, 326, 332,
Index 503
368, 373, 390, 391, 392, 402, 405, 417, 418, 423,
430, 435, 437, 439, 443, 461, 468, 492, 493, 495,
E
498, 502
economical concerns, xv, 365, 366
desorption, 25, 285, 523
editors, 413
destruction, 280, 522
Egypt, 279
developed countries, 436
electrochemistry, 285
deviation, 287
electrodes, 31
DFT, 51, 80, 81, 95, 96, 157, 158, 160, 161, 162,
electrolyte, 27
163, 166, 403
electromagnetic waves, 372
diabetes, 266
electron, 4, 27, 50, 56, 69, 83, 92, 114, 115, 150,
diacrylates, 473
151, 159, 160, 176, 196, 238, 241, 249, 251, 254,
dialysis, 377
266, 268, 297, 346, 351, 387, 388, 396, 397, 404,
diamines, 261, 305, 331
421, 425, 426, 428, 429, 470, 488, 494, 496, 522,
dielectric constant, 226
526, 527, 534, 536, 538, 544, 546, 549, 556
dienes, 339, 387, 419, 425, 429, 501, 503
electron cyclotron resonance, 4
diffraction, 176, 183, 185
electron microscopy, 176
diffusion, 183, 318, 370, 371
electron pairs, 426
diffusivities, 177
electronic spectroscopy, xiv, 265
diffusivity, 212
electrons, 425
dihydroxyphenylalanine, 167
electrophoresis, 285
dimerization, 355, 525
electrospinning, 21
dimethacrylate, 22, 198
elongation, 313, 445
dimethylformamide, 24, 288, 390, 452
elucidation, 116
dimethylsulfoxide, xvi, 267, 435, 449
emission, 176
discrimination, 74
employment, 6
discs, 268
emulsions, 224, 372
dispersion, 9, 22, 25
enantiomers, 61, 74, 81
displacement, 387, 544
enantioselective synthesis, 387
disposition, 81
enantioselectivity, xii, 65, 69, 76, 78, 79, 80, 144,
dissociation, 81, 421, 423, 456, 462, 509, 525
146, 147, 151, 161, 179, 289, 291, 296, 299, 300,
distillation, xiii, 209, 210, 211, 214, 225, 280
302, 303, 304, 305, 306, 307, 318, 319, 320, 321,
distilled water, 267, 268
322, 324, 327, 328, 329, 330, 332, 335, 336, 338,
distortions, 276
347, 402, 404, 490
distributed computing, 163
encapsulated, 523, 524, 525
diversity, 151, 467
endothermic, 197
DMAP, xvi, 435, 437, 438, 439, 444, 445, 446, 447,
energy, 155, 157, 161, 162, 177, 210, 213, 219, 225,
449
366, 367, 370, 371, 405, 462
DMF, 24, 189, 190, 200, 202, 214, 256, 291, 303,
energy consumption, 210, 367
306, 391, 526, 527, 529, 530, 546, 548, 549, 550,
engineering, 175, 202, 203, 450
552
England, 32, 168
DNA, 30
entanglements, 287
donor, 527, 536, 538, 546, 549, 556
entropy, 496
dosage, 441, 445
environment, xvii, 521, 523, 528
double bonds, 69, 349, 418, 421, 423
environmental impact, 211, 212, 366
dream, 31
enzymatic, 532
drug delivery, 437
enzymes, xi, 48, 49, 143, 148, 211, 214, 266, 283,
drug discovery, 164
289, 450, 536
drug release, 178
EPR, 115, 128, 134, 285, 524
drugs, xv, 212, 213, 351, 365, 373, 382, 383
equilibrium, 12, 51, 179, 204, 386, 422
drying, 23, 176
equipment, 227, 372
DSC, 197, 285
ESI, 285, 286, 304, 359
dyes, xiii, xv, 23, 49, 233, 365, 367, 368
ester, 23, 30, 179, 182, 206, 226, 228, 250, 297, 350,
377, 394, 405, 423, 437, 445, 505
504 Index
esters, xiii, xvi, 213, 222, 223, 228, 233, 235, 248, fluorescence, 193, 285
249, 250, 251, 252, 254, 262, 296, 387, 405, 407, fluoxetine, 146
417, 418, 421, 425, 446, 489, 498 food products, 213
ethanol, 4, 5, 11, 19, 21, 25, 28, 31, 65, 173, 198, Ford, 142
213, 267, 291, 293, 306, 385, 386, 450 formaldehyde, 6, 24, 29
etherification, 368 formamide, 526
ethers, 214, 223, 228, 368, 381, 383, 387, 402, 403, formula, 52, 64, 74, 159, 444
424, 426, 536, 538, 551, 555 fouling, 348
ethyl acetate, xiii, 182, 209, 217, 223 foundations, 162
ethylbenzene, 524, 525, 526, 529, 530, 531, 532, Fourier Transformed Infra-red spectroscopy, xiv,
533, 534, 536, 537, 538, 539, 540, 541, 542, 543, 265
545, 546, 547, 548, 549, 550, 551, 552, 553, 554, fragments, 15, 352, 525
555, 556, 557, 558, 559, 560, 561 fragrant properties, xvi, 418
ethylene, x, xi, 18, 20, 28, 107, 108, 109, 110, 111, France, 33, 37, 38
113, 114, 116, 117, 118, 119, 120, 121, 122, 123, free energy, 383
124, 125, 126, 127, 128, 130, 131, 132, 134, 135, free radical, 522, 524, 526
137, 138, 152, 198, 525 freezing, 176
ethylene glycol, 22, 198 FTIR, 268, 270, 272, 276
ethylene oxide, 28, 525 functionalization, 294, 313, 351, 352, 437, 448, 451
ethylene polymerization, x, xi, 107, 108, 109, 110, furan, 17, 481
111, 114, 116, 118, 120, 121, 123, 124, 125, 127,
128, 130, 131, 132, 134, 135, 138
G
European Union, 436
GCE, 28
evaporation, 27, 216, 426
gel, 3, 15, 22, 173, 174, 175, 176, 177, 178, 179,
evolution, 528
180, 183, 184, 185, 188, 189, 190, 191, 192, 193,
excitation, 371
194, 195, 197, 198, 199, 200, 201, 202, 203, 204,
exercise, 266
205, 207, 338, 523
experimental condition, xv, xvi, 366, 435
gel formation, 183, 185
expertise, 161, 366
gelation, 15, 175, 176, 178, 179, 183, 187, 191, 197,
exposure, 193, 371
203, 204, 205, 206
extraction, xiii, 25, 179, 209, 210, 211, 212, 216,
geometry, 76, 158, 164, 467, 536
217, 221, 223, 224, 225, 228, 268, 280, 370, 384,
Germany, 98, 229, 511
422, 438, 440
glass transition, 287
F glass transition temperature, 287
glasses, 4
fabrication, xiv, 266 glucose, 12, 29, 436
fatty acids, 222 glutamate, 28
FDA, 213 glycerin, 212
fiber, 3, 205 glycerol, ix, xii, 209, 212, 213, 214, 215, 216, 217,
fibers, 6, 20, 205, 206, 451 218, 220, 221, 222, 223, 224, 225, 226, 227, 228
fillers, 1, 6 glycine, 300, 377
films, 21, 26, 27, 30 glycol, 13, 22
filtration, xiv, 26, 30, 177, 187, 193, 218, 267, 279, glycoside, 203
303, 321, 324, 327, 346 gold nanoparticles, 28
financial support, 166, 203, 449 GPC, 327
fine tuning, 305 granules, 23
first generation, 20, 299, 307, 315, 321, 356, 377 graphite, 12, 19
fixation, 155, 294 grass, xvi, 418
flame, 5, 6, 15, 21, 269 greening, 366
flavor, 61 Grignard reagents, 52, 53, 483
flexibility, xiv, 218, 266, 276, 317, 457 groups, 526, 544
fluid, 189, 212, 229, 230 growth, 532, 538, 546, 547, 552
fluid extract, 230 growth rate, 6
Index 505
Guangdong, 449 hydrogenation, xi, xii, xiii, xiv, xv, xvi, 3, 8, 14, 19,
Guangzhou, 173, 435, 438 25, 26, 144, 145, 147, 148, 152, 165, 166, 209,
215, 224, 227, 228, 280, 288, 289, 290, 291, 293,
H 294, 296, 297, 298, 299, 300, 301, 302, 303, 304,
305, 306, 307, 308, 310, 347, 359, 417, 418, 419,
hafnium, 5
420, 421, 422, 423, 424, 425, 427, 430, 499
halogen, 57, 58, 114, 121, 451, 522
hydrolysis, 5, 91, 92, 179, 182, 206, 368, 450
halogenated, 522
hydroperoxides, 49, 50, 66, 67, 80, 92, 522, 526
halogens, 551
hydrophilicity, 394
hardness, 6
hydrophility, 523
Hawaii, 32, 38
hydrophobic, 523
hazards, 49
hydrosilylation, xii, 18, 144, 310, 349
H-bonding, 182, 183, 187, 189, 191, 193, 197, 539
hydrothermal, 523
HDPE, 23
hydrothermal process, 5
heating rate, 268
hydroxide, 5, 9, 381, 390, 438, 439
height, 192
hydroxyapatite, 3, 13, 24
hemicellulose, 450
hydroxyl, xvii, 16, 26, 49, 179, 191, 226, 292, 401,
heptane, 111, 112, 117, 119, 131, 132, 134, 135, 423,
436, 437, 441, 442, 444, 445, 446, 448, 449
494
hydroxyl groups, xvii, 16, 191, 292, 436, 437, 442,
heterogeneous, 521, 524
444, 445, 446, 448, 449
heterogeneous catalysis, xii, xiv, 2, 7, 173, 178, 219,
hyperbranched polymers, 29, 280
277, 279, 281, 476, 521
hypothesis, 488
heterogeneous systems, 275, 276, 281
hexane, 15, 290, 309, 379, 380, 381 I
hexenoic acids, xv, xvi, 417, 418, 419, 425
high density polyethylene, 23 ideal, 162, 210, 211, 242, 281, 316, 509
high oxidation state, x, 48 image, 192, 196, 198, 274
high-capacity virtual ligand libraries, xii, 144 images, 181, 182, 186, 188, 190, 192, 195, 199, 200,
high-molecular compounds, 283 274
high-throughput experimentation, xii, 144, 167 imagination, 96
histidine, 182 imino, vii, ix, x, xi, 107, 108, 109, 110, 112, 113,
homogeneity, 285 114, 115, 116, 118, 120, 122, 124, 125, 128, 129,
Homogeneous catalysts, iv, ix, 47 130, 134, 137, 138, 139, 140, 332
homogenous, 522 imitation, xvi, 418
homolytic, 522, 526, 560 immobilization, 205, 357, 425
host, 27, 436 impregnation, 9, 17, 21, 24, 28
HTE, xii, 144, 165, 167 impurities, 25, 177, 285, 286
hybrid, 204, 280 in silico screening, xii, 144, 164
hydrazine, 21 in situ, 526, 529, 532, 561
hydrides, 227 inactive, 531, 539, 546
hydrocarbons, 11, 54, 214, 387 India, 36, 233
hydrogels, 174, 179, 203, 205, 452 indium, 31
hydrogen, 4, 6, 16, 25, 26, 30, 49, 51, 54, 65, 82, 91, induction, 52, 63, 75, 81, 147, 153, 179, 316, 321,
148, 161, 174, 176, 179, 180, 203, 205, 206, 213, 377, 402, 403, 404, 539
227, 228, 248, 269, 273, 283, 300, 304, 307, 309, induction period, 539
342, 393, 397, 398, 400, 418, 419, 420, 421, 422, Industrial, 230, 356, 413, 450
423, 425, 428, 429, 437, 465, 529, 535, 536, 538, inert, 523
543, 545, 548, 551 infancy, 202
hydrogen abstraction, 54 inhibition, xi, 108, 110, 116, 509, 526, 561
hydrogen atoms, 161 inhibitor, 3, 556, 558, 560
hydrogen bonds, 176, 283, 535, 536, 543, 545 initiation, 522, 526, 537, 546, 560
hydrogen cyanide, 179, 180, 206 insertion, 13, 116, 236, 238, 248, 250, 255, 256, 257,
hydrogen peroxide, 49, 65, 82, 91, 342, 397, 398, 527
400 insulators, 8
506 Index
integration, 450
interaction, 524, 533, 534, 537, 555, 556
L
interface, 217, 372, 374, 385, 399
lack of control, 372
intermolecular interactions, 524
lactic acid, 20
interphase, 399
landscape, 163
interval, 546, 560
lanthanum, 5
intrinsic viscosity, 121, 138, 285, 286, 287, 359, 439,
leaching, 316, 352, 357, 422, 423, 456, 509
440
lead, xiv, xvii, 56, 76, 82, 92, 96, 174, 191, 210, 279,
inversion, 193
280, 282, 283, 348, 521, 539, 544, 547, 550
iodine, xvi, 308, 435, 436, 437, 438, 440, 441, 442,
ligands, xvii, 521, 522, 524, 525, 526, 527, 528, 536,
446, 447, 449, 452
538, 544, 546, 550, 551, 554, 556
ion implantation, 3
light scattering, 191
ion-exchange, 398, 399
lignin, 436
ionic, 535
limitations, 523
ionic liquids, xvi, 4, 6, 8, 15, 20, 25, 61, 211, 212,
linear, 523
243, 435, 436, 437, 441, 451, 535
linear macromolecule, 287
ionization, 269, 285
linear molecules, 287
ions, 3, 31, 197, 198, 211, 260, 367, 384, 388, 394
linear polymers, 286, 287, 288
IR spectra, 439, 446, 447
liposomes, 27
IR spectroscopy, 159, 339
liquid phase, 174, 176, 210, 228, 370, 371, 372, 374,
iridium, 25, 33, 307
382, 396, 406, 412
iron, 4, 6, 49, 108, 109, 112, 113, 114, 115, 118, 120,
liquids, xvi, 4, 6, 8, 15, 20, 25, 61, 202, 203, 210,
122, 123, 124, 125, 128, 130, 137, 140, 160, 522,
211, 212, 216, 229, 243, 435, 436, 437, 441, 451,
524, 531
535
irradiation, xv, 8, 28, 30, 88, 89, 226, 366, 371, 372,
lithium, 310, 452
373, 381, 383, 384, 389, 400, 404, 405, 407, 412
loading, 524
IR-spectroscopy, 527
localization, 524
isobutylene, 405
low oxidation, x, 48
isolation, xiii, 177, 209, 282, 314, 461, 524
lubricants, xv, 365, 368
isomerization, 19, 31, 310
Luo, 27, 44, 169, 206, 411, 450, 452, 512, 513, 514
isomers, 288, 418, 425, 430, 472
lying, x, 48, 63
isoprene, 405
lysine, 204, 314
Israel, 209
IV, vii, xiv, 265, 266, 267, 269, 271, 274, 317, 323, M
429, 457, 460
macromolecules, 280, 281, 283, 285, 286, 437
J
magnesium, 6, 9, 483
magnet, 194
Japan, 414, 432
magnetic properties, 176
K magnetism, 6, 194
magnitude, 122, 313
ketones, xiii, 11, 26, 31, 49, 145, 149, 152, 233, 235, maintenance, 539
237, 238, 239, 243, 244, 245, 257, 259, 260, 301, majority, 50, 92, 165, 210, 251, 371, 522
302, 303, 304, 305, 353, 354, 368, 422, 489, 490, MALDI, 285, 286, 339
498 maltose, 30
kinetic curves, 111, 554 manganese, 2, 3, 49, 340
kinetic model, 51, 94 manufacturing, xv, 365, 368, 397
kinetic regularities, 547, 551 MAO, x, xi, 107, 108, 109, 110, 111, 112, 113, 114,
kinetic studies, 16, 23, 51, 408 115, 116, 117, 118, 119, 120, 121, 122, 123, 124,
kinetics, xv, 51, 83, 96, 366, 374, 399, 401, 408, 559 125, 126, 127, 128, 129, 130, 131, 132, 134, 135,
KOH, 11, 215, 222, 374, 375, 376, 377, 385, 386 136, 137, 138, 139, 502
Korea, 279 mapping, 163
MAS, 195, 437, 440, 447, 448, 449
Index 507
mass spectrometry, 285, 286, 298 minors, 269, 277

matrix, 1, 4, 6, 7, 12, 15, 23, 26, 29, 174, 176, 189, mixing, 20, 122, 134, 147, 194, 200, 223, 228, 303,
285, 342, 352 306, 310, 314, 422, 438
mechanical properties, 8 MMA, 22, 29
mechanistic explanations, 522 MNDO, 158, 167
media, xiv, 30, 148, 205, 210, 212, 229, 258, 279, Mo catalysts, ix, x, 48
316, 371, 419, 437, 451 model system, 266, 310
median, 74 modeling, 536
melt, 269, 280, 287 modelling, xi, xii, 144, 150, 158, 163, 165, 176
melting, xiv, 15, 53, 265, 269 models, x, xii, 48, 52, 144, 154, 156, 160, 163, 165,
membranes, 8, 377 261, 320, 403, 522, 528
memory, 27 modules, 314
Mendeleev, 432 modulus, 177
mesoporous materials, 315 moisture, x, xvii, 48, 92, 93, 238, 455, 456, 457, 464,
messengers, 532 471, 486, 495
metabolic disorder, 382 molar ratios, 329
metal complexes, 189, 368, 523, 525, 526 mole, 29, 531, 532
metal ion, 30, 176, 192, 202, 269, 437, 544 molecular dynamics, 158
metal ions, 30, 176, 192, 437 molecular mass, 203, 204, 283, 287
metal nanoparticles, 1, 24, 26, 29 molecular oxygen, 31, 49, 74, 497, 498, 554
metal oxides, x, 2, 48 molecular structure, xi, 109, 137, 144, 175, 202
metallic nanoparticle-polymer, ix, 1 molecular weight distribution, x, 107, 108, 109, 113
metallocenes, 109 molecules, xv, xvii, 2, 12, 16, 24, 152, 158, 161, 162,
metallogels, xii, 173, 193, 200, 202 163, 164, 174, 175, 177, 178, 179, 203, 216, 227,
metalloporphyrins, 525 247, 257, 281, 283, 287, 366, 368, 377, 380, 392,
metals, ix, 1, 2, 3, 5, 6, 70, 154, 371, 456, 457, 535, 421, 423, 437, 455, 461, 502, 535
536 molybdenum, x, 4, 48, 49, 54, 56, 65, 74, 88, 344
meter, 372 molybdoenzymes, x, 48
methanol, 7, 20, 27, 30, 57, 195, 221, 222, 224, 234, MOM, 206
267, 291, 299, 303, 305, 320, 321, 324, 338, 346, momentum, 210
419, 428, 429 monolayer, 30, 324
methodology, 235, 372, 387, 390, 391, 392, 405, 408 monomers, xv, 137, 285, 313, 365, 367, 368
methyl group, 404, 471 morphine, 145
methyl methacrylate, 22, 453 morphology, 191, 193, 203, 285
methyl phenyl sulfide, xiv, 265, 267, 274, 275, 276, Moscow, 521
277 motif, 74, 237
methylalumoxane, x, 107, 115 MoVI complexes, x, 48, 49, 50, 62, 63, 65, 73, 81
methylene blue, 23 MP, 526, 527, 534, 538, 542, 544, 554, 556, 558,
methylene chloride, 65 560
Mexico, 32 MPA, 546
mice, 261 multiwalled carbon nanotubes, 14
micelles, 535, 540, 549 MWD, 113, 114, 116, 117, 118, 120, 121, 122, 123,
microcrystalline, 183 125, 127, 128, 129, 134, 135, 136, 138, 139
microemulsion, 15, 23
microenvironment, 523, 524
N
micrometer, 5, 174, 187
N/O ligands, 78
microorganism, 213
NAD, 148
microscopy, 285
nanocomposites, 2, 3, 4, 5, 6, 7, 26, 29, 32
microspheres, 13
nanocrystals, 3, 5, 25
microwave heating, 225, 389
nanofibers, 5, 7, 9, 20, 206
microwave radiation, 83, 373
nanomaterials, 1
migration, 425
nanometer, 5, 174, 202
Ministry of Education, 166
nanometer scale, 174
508 Index
nanoparticles, 1, 2, 3, 4, 5, 6, 7, 8, 14, 19, 23, 25, 26,

28, 31, 33, 194, 195, 216, 292, 293
O
nanorods, 30
obstacles, 69
nanostructured materials, 32
octane, 383
nanostructures, 4, 6, 27, 30, 179
o-dichlorobenzene, 377
nanowires, 28
OH, 5, 11, 15, 25, 26, 65, 80, 273, 274, 292, 370,
naphthalene, 15, 23, 250, 251, 262, 375, 376, 465
485, 486, 537
N-bromosuccinimide, xvi, 435, 436, 437, 452
oil, xvi, 83, 203, 214, 217, 221, 222, 226, 418
NBS, xvi, 435, 437, 438, 442, 443, 444, 447, 448,
olefin epoxidation, x, 48, 50, 52, 55, 58, 61, 62, 63,
449, 452
65, 66, 74, 78, 79, 80, 85, 87, 92, 95, 96, 344
negative effects, 300
olefins, x, 10, 20, 48, 55, 57, 66, 67, 70, 71, 74, 75,
neglect, 167
76, 77, 80, 92, 96, 137, 234, 257, 309, 312, 314,
Netherlands, 358
351, 353, 355, 387, 388, 396, 397, 402, 429, 471,
neurotoxicity, 509
497, 498, 499
next generation, 286
oleic acid, 5
NH2, 27, 305
oligomerization, 114, 125
NHC, xvii, 455, 464, 466, 467, 468, 469, 472, 473,
oligomers, 109, 113, 501
474, 483, 485, 487, 488, 490, 492, 497, 499, 503,
operations, 367
509
opportunities, 408
N-heterocyclic carbenes, xvii, 455, 456, 457, 461,
optical properties, 3, 7
462, 463, 464, 467, 470, 474, 477, 483, 485, 487,
optimism, 175
488, 489, 491, 494, 497, 503, 509
optimization, xi, 143, 155, 471
nickel, 3, 7, 108, 215, 237, 483, 527, 529, 532, 534,
organ, x, xiii, 18, 48, 52, 57, 82, 96, 164, 206, 233,
536, 537, 538, 540, 542, 543, 544, 545, 546, 548,
234, 259, 350, 418, 430
559, 561
organic, 535
nicotinamide, 262
organic compounds, xiii, 48, 62, 148, 209, 211, 214,
niobium, 4
216, 227, 228, 392
nitrobenzene, 23, 26
organic ligands, ix, 47, 74, 192
nitrogen, 6, 23, 48, 109, 113, 176, 270, 297, 323,
organic mediums, 11
368, 392, 394, 396, 483, 494
organic polymers, 177
nitrogenase, 52, 266
organic solvent, 535
nitroso compounds, 49
organic solvents, 27, 29, 174, 189, 193, 195, 197,
NMR, xvii, 15, 81, 93, 94, 115, 119, 122, 126, 128,
204, 205, 212, 214, 216, 218, 223, 224, 225, 226,
133, 137, 159, 163, 167, 176, 187, 193, 195, 197,
228, 242, 243, 287, 288, 298, 308, 327, 354, 389,
205, 268, 273, 276, 285, 298, 312, 339, 425, 436,
419
437, 440, 447, 448, 449
organogels, xii, 173, 174, 179, 182, 197, 203
noble metals, ix, 1
organomagnesium compounds, 483
nonane, 385, 386, 468
organotin compounds, 237
non-steroidal anti-inflammatory drugs, 237
osmium, 24
norbornene, 355, 400, 501
overlap, 167
Northern Ireland, 173
Oxidation catalysis, x, 47
novel materials, 351
oxidation catalysts, x, 48
nuclear, 527, 550
oxidation products, 49, 66, 92, 269, 523, 540, 546,
nuclear magnetic resonance, 167, 437
550, 551, 554
Nuclear Magnetic Resonance, xiv, 265, 268
oxidation rate, 526
nucleation, 372
oxidative, 522, 526, 528, 538, 548
nuclei, 159
oxidative destruction, 522
nucleophiles, xiii, 233, 234, 235, 247, 248, 249, 250,
oxide, 525
262, 392, 405, 485, 501
oxide nanoparticles, 7
nucleophilicity, 342, 485
Oxovanadium, vii, xiv, 265, 266, 267, 269, 271, 274
null, 298
oxygen, 4, 5, 6, 12, 27, 48, 51, 75, 77, 78, 79, 81, 82,
87, 228, 262, 266, 267, 268, 274, 398, 425, 486,
522, 524, 525, 529, 545, 554
Index 509
oxygenation, 525, 528, 529, 532, 534, 551 play, 535

PMMA, 29, 198, 199
P poison, 426
Poland, 37
Pacific, 38
polar groups, 109
Palladium-catalyzed carbonylation reactions, xiii,
polarity, 223, 228, 523
233, 262
polarization, xvi, 436
PAN, 6
pollution, 211, 347, 366, 367, 368
parallel, 63, 66, 86, 89, 157, 527, 531, 538, 540, 546,
poly(methyl methacrylate), 29
547, 555, 560
polyamides, 261
parallelism, xi, 144, 538
polybutadiene, 401, 406
parameter, 538, 540, 543, 544, 545, 547, 550, 552,
polycondensation, 261
553, 555, 558
polydispersity, 112, 121, 127, 285
particles, xvii, 521, 523, 526, 538, 539, 545
polyesters, 213, 261, 287, 339
partition, 394, 406
polyether, 287, 288, 291, 314, 320, 536
passivation, 316, 534
polyethylene, 525
patents, 50
polyimide, 30
pathways, 48, 88, 89, 91, 95, 146, 285
polyisoprene, 22
PCA, 164, 167
polymer, ix, xii, 1, 5, 6, 13, 21, 27, 28, 48, 113, 114,
PCP, 474
116, 120, 121, 124, 125, 129, 136, 137, 173, 178,
PCR, 167
192, 193, 195, 197, 198, 202, 204, 205, 206, 207,
perfume chemistry, xv, 417
247, 280, 281, 285, 293, 299, 313, 317, 318, 327,
permeation, 327
329, 336, 337, 338, 347, 348, 350, 355, 357, 368,
peroxide, 49, 50, 51, 52, 93, 397, 398, 524, 534, 554,
373, 436, 469, 476, 523, 524, 525
555
polymer chain, 124, 136, 525
petroleum, 176
polymer composites, ix, 1
pharmaceutical industry, ix, 47, 69, 164
polymer matrix, 1, 317
pharmaceuticals, xiii, xiv, xv, 49, 61, 145, 212, 233,
polymer molecule, 120, 121
234, 247, 266, 365, 367, 368, 387, 444, 461, 486
polymer synthesis, 368
phase transfer catalysis, xv, 365, 367, 382, 394, 405
polymeric catalysts, 302, 303
phenol, 7, 8, 14, 23, 24, 82, 252, 254, 527, 530, 539,
polymeric materials, 280
540, 544, 545, 547, 550, 556, 558, 561
polymeric products, 108
phenol oxidation, 7
polymerization kinetics, 139
phenolphthalein, 439
polymerization process, 109, 116, 287
phenomenology, 560
polymerization temperature, 110, 119, 125, 127, 128,
phenoxycarbonylation, xiii, 233
130, 131, 134, 135, 136, 138, 139
phenyl esters, 262
polymerization time, 112, 113, 116, 117, 120, 123,
phenylalanine, 13
124, 127, 129, 130, 134, 139, 140
PhOH, 539, 543, 551, 554, 556, 557, 558, 559, 560,
polymers, 2, 27, 28, 31, 108, 109, 113, 120, 124,
561
129, 136, 138, 174, 192, 197, 203, 204, 205, 280,
phosphorus, 144, 145, 146, 147, 148, 150, 152, 155,
287, 318, 327, 329, 335, 336, 355, 356, 437, 444
156, 157, 159, 160, 161, 163, 200, 290, 312, 350,
polymorphism, 175, 203, 205
394
polypropylene, 311
physical properties, 210, 212, 229, 287, 536
polystyrene, 5, 12, 27, 29, 291, 313, 314, 317, 327,
physicochemical, 527, 536
329, 335, 336, 337, 357, 422, 525
physicochemical methods, 527, 536
pore, 523
physics, 202
porous materials, 176
physiology, 532
porphyrins, 339, 522, 524
plants, 210, 450
portfolio, 457
plasticity, 4
Portugal, 38, 47, 104
plasticizer, 213, 383
potassium, 216, 381, 383, 386, 388, 390, 391, 406,
plastics, 49
420, 422, 438
platform, 355, 456, 509
platinum, ix, 1, 20, 26, 268, 509
510 Index
precipitation, xiv, 31, 176, 279, 302, 304, 305, 320, radius, 157
348, 350, 357, 537 range, 532
preparation, xv, xvi, 21, 53, 69, 74, 78, 88, 91, 92, rational design, xi, 144, 149, 158, 165, 178, 202
108, 140, 176, 204, 235, 241, 242, 246, 252, 254, rationality, 175
262, 263, 266, 267, 292, 313, 351, 373, 378, 387, raw materials, 436
417, 418, 422, 426, 430, 525 reactant, xiii, 25, 209, 213, 221, 226, 228, 293, 367,
prevention, 210 380, 399
principal component analysis, 167 reactants, xiii, xv, 209, 210, 212, 216, 223, 224, 226,
principal component regression, 167 318, 365, 367, 371, 379, 380
probability, 527, 548, 549, 551 reaction center, 2, 320, 404, 522
probe, 75, 342, 440 reaction mechanism, 51, 52, 65, 161, 165, 185, 239,
project, 163 374, 385, 420, 423, 424, 524
proliferation, 509 reaction medium, 82, 137, 210, 213, 214, 216, 219,
propagation, xi, 108, 110, 115, 117, 123, 124, 129, 221, 222, 243, 300, 315, 437, 451, 452, 486
136, 140, 175, 314, 527, 537, 547 reaction rate, xv, 21, 117, 129, 177, 211, 217, 282,
propane, 17, 155, 156, 311 311, 350, 365, 367, 371, 373, 375, 376, 379, 381,
propionic anhydride, 437 382, 385, 387, 405, 423, 522, 539
propylene, 18, 28, 116, 213, 284, 285, 287, 288, 525 reaction temperature, xv, xvi, 65, 93, 125, 211, 225,
protection, 523 257, 314, 342, 365, 367, 372, 392, 435, 440, 441,
proteins, 283 442, 443, 445, 492
protons, 273 reaction time, xvi, 56, 65, 89, 93, 123, 129, 224, 277,
prototypes, 162 304, 305, 336, 346, 350, 371, 372, 373, 378, 389,
PTC, xv, 365, 367, 368, 369, 370, 371, 372, 373, 392, 395, 435, 465, 466, 555
374, 375, 377, 378, 379, 380, 382, 383, 384, 385, reactive sites, 179, 448
387, 389, 390, 391, 392, 394, 395, 397, 398, 399, reactivity, xi, 4, 31, 51, 52, 54, 108, 110, 116, 117,
400, 401, 402, 405, 407 118, 124, 128, 134, 136, 139, 287, 301, 305, 307,
pulp, 451 314, 315, 321, 327, 335, 342, 346, 352, 369, 384,
purification, 212, 217, 221, 228, 284, 286, 339, 367, 394, 399, 401, 407, 408, 457, 465, 492, 501, 523,
426 531
purines, 48 reading, 96
purity, 225, 284, 285, 286, 396 reagents, xiv, 49, 134, 185, 196, 210, 219, 238, 259,
PVC, 29 267, 280, 281, 290, 327, 330, 334, 346, 355, 362,
PVP, 8, 16, 23, 28 366, 367, 371, 383, 407, 437, 457, 461, 483, 485,
pyridine ligands, x, 107, 109 486, 505, 523
pyrimidine, 245, 261, 471 reality, 162, 284
pyrolysis, 5, 21, 24 reasoning, 162
pyromellitic dianhydride, 26 recognition, 174, 205, 536
recycling, xiii, 61, 177, 209, 211, 221, 226, 228, 266,
Q 281, 293, 300, 303, 304, 347, 351, 356, 357
redistribution, 527, 550
quantum mechanics, 167
redox, 522
quaternary ammonium, 367, 369, 374, 378, 384, 386,
reference system, 299
387, 399, 400, 535, 536, 539, 544, 549
regenerate, 235
quercetin, 528
regeneration, 7, 399, 496
R regioselectivity, 49, 82, 217, 237, 256, 314, 315,
339, 347, 503
race, 61, 62, 75, 368 regression, 164, 167
radiation, 3 regulation, xviii, 521
Radiation, 38 rejection, xii, 144
radical formation, 526 relevance, x, 48, 61, 66, 457, 496
radical reactions, 442, 523 reliability, 165
radicals, 282, 522, 535, 539, 554, 555, 556 relief, 355
radioactive carbon monoxide, xi, 108, 110 Reppe and Heck, xiii, 233
Index 511
reputation, 154 silicon, 21, 485, 523

requirements, 69, 158, 161, 212, 408 silver, 23, 426, 429, 458
researchers, xv, 266, 365, 368, 408 similarity, 529
residues, 151, 436, 438, 439, 450 simulation, 205, 285
resistance, 57, 374, 405 SiO2, 5, 7, 12, 17, 21, 25, 26, 30, 342, 344
resolution, 69, 73, 74, 76, 216, 226, 440, 498 sites, 525, 536
resources, 158, 162, 213, 449 skeletal muscle, 3
responsiveness, 176, 203 skeleton, 283, 296
resveratrol, 391 sodium, 12, 17, 21, 28, 30, 221, 244, 267, 350, 367,
Rh complexes, xi, 144, 296, 312, 314, 420 378, 380, 382, 390, 396, 400, 404, 405, 406, 438,
rhenium, 6, 49 440
rheology, 174, 205 sodium hydroxide, 21
rhodium, 14, 289, 291, 293, 296, 297, 298, 304, 310, sol-gel, 15, 26, 185, 189, 204, 342
314, 315, 316 solid phase, 370
rings, 14, 109, 114, 120, 121, 129, 289, 492 solid state, 287
ROOH, xvii, 50, 521, 522, 535, 537, 538, 540, 555 solubility, ix, 47, 53, 211, 216, 223, 224, 227, 228,
room temperature, 15, 24, 26, 27, 29, 65, 82, 93, 115, 242, 269, 281, 283, 287, 299, 300, 302, 317, 348,
204, 243, 244, 267, 297, 298, 313, 320, 335, 340, 351, 356, 357, 382, 426, 451, 508
346, 350, 390, 392, 418, 419, 420, 421, 424, 450, solvation, 216
464, 465, 468, 469, 483, 484, 493, 495, 503 solvent, 535, 536, 550, 551
Royal Society, 409 solvent molecules, 191
Ru catalysts, ix, xi, 144, 291, 424 solvents, xiii, xv, 49, 61, 62, 65, 89, 187, 189, 195,
Russia, 33, 521 198, 209, 210, 211, 212, 214, 216, 219, 225, 226,
Russian Academy of Sciences, 557 228, 229, 267, 288, 307, 365, 367, 371, 376, 420,
ruthenium, 8, 49, 282, 291, 300, 304, 422, 428, 525 424, 426, 437, 440, 525
sorption, 523
S spatial, 536
speciation, 92, 94
salts, xvi, 17, 187, 203, 204, 205, 206, 211, 214, 216,
species, xvii, 3, 7, 25, 31, 33, 51, 62, 65, 74, 79, 80,
220, 239, 240, 245, 368, 369, 377, 384, 387, 389,
83, 88, 92, 93, 94, 108, 115, 122, 127, 148, 160,
395, 399, 400, 407, 417, 418, 458, 463, 464, 470,
163, 164, 165, 173, 176, 195, 236, 238, 245, 251,
471, 486, 535, 536, 544, 545, 549, 555, 556
266, 282, 285, 294, 371, 372, 396, 419, 421, 456,
saturation, 426
458, 460, 470, 476, 488, 496, 498, 499, 521, 524,
scaling, 13
525, 529, 531, 535
scandium, ix, 1, 2, 4
specific surface, 177
scarcity, 164
specifications, 212
scattering, 3, 176, 205
spectrophotometry, 544
Schiff bases, xiv, 265, 266, 267, 269
spectroscopy, xiv, 51, 92, 93, 115, 159, 167, 197,
second generation, 26, 304, 305, 307, 313, 314, 317,
265, 285, 298, 447, 524, 527
508
spectrum, 544, 554
seizure, 261
spin, 62, 115
self-assembly, 174, 182
sponge, 198, 199
sensing, 30, 178
Spring, 38
sensitivity, 18, 163, 164, 212, 405, 486
stability, 522, 523, 524, 543
sensors, 7
stabilization efficiency, 10
shape, x, 22, 29, 47, 154, 174, 281, 283, 285, 287
stabilizers, 4, 10, 16, 26
shear, 177
stable complexes, 48, 548
shock, 371
stages, xvii, 521, 532, 533, 540, 546, 547, 554, 556,
shock waves, 371
559
signals, 128, 134, 448
starch, 452
silanol groups, 526
states, 161, 457, 476
silica, 3, 7, 8, 14, 21, 25, 26, 312, 313, 328, 338, 342,
statistics, 284
344, 347, 351, 352, 353, 354, 355, 357, 523, 524,
525
512 Index
stereoselectivity, xi, 18, 143, 146, 152, 161, 185, TEM, 176, 179, 181, 187, 188, 189, 190, 191, 192,
317, 337, 347, 377, 389, 408 194, 195, 198, 199, 200, 202
steric, 523, 529, 539, 548, 551 temperature, 5, 6, 16, 26, 53, 57, 61, 80, 82, 127,
steroids, 69 128, 130, 134, 135, 136, 139, 140, 161, 174, 176,
storage, 25, 26, 177, 214, 456 178, 179, 185, 204, 211, 212, 239, 245, 256, 267,
stretching, 159, 270, 277, 446 268, 269, 297, 307, 314, 335, 346, 367, 400, 404,
strong interaction, 2 405, 408, 420, 421, 422, 440, 443, 445, 464, 472,
structural changes, 159, 176, 535 483, 484, 503, 525
structural characteristics, 385 TEOS, 21
styrene, 3, 10, 14, 20, 24, 64, 65, 79, 93, 217, 218, testing, xi, 82, 96, 143, 160
223, 224, 294, 311, 312, 316, 341, 344, 395, 400, tetrabutylammonium bromide, 374, 378, 381, 392,
470, 471, 472, 474, 498, 535 394, 399
substitutes, 494 tetrahydrofuran, 8
substitution, 76, 150, 151, 161, 215, 216, 218, 226, TGA, 268
296, 346, 347, 350, 367, 378, 384, 437, 452, 501, therapy, 509
539 thermal analysis, 274
substrates, x, xi, xii, xvii, 13, 20, 26, 48, 49, 70, 74, thermal decomposition, 4, 5, 16
82, 92, 93, 96, 143, 151, 153, 209, 211, 221, 224, thermal stability, xi, 53, 88, 108, 110, 112, 118, 130,
234, 243, 246, 247, 248, 249, 251, 255, 258, 283, 138, 139
297, 305, 307, 314, 321, 330, 356, 367, 389, 408, thin films, 4, 21
455, 462, 463, 464, 465, 467, 468, 469, 471, 474, thioamides, xiii, 233
483, 485, 487, 492, 494, 495 thiocarbonylation, xiii, 234
sugarcane, xvi, 435, 449, 450, 452 three-dimensional model, 164
sulfate, 28, 267 tin, 31, 477
sulfonamides, 494 tin oxide, 31
sulfur, 48, 213, 483 titania, 18
sulfuric acid, 288 titanium, 2, 3, 321
Sun, 10, 39, 42, 97, 101, 102, 142, 173, 362, 412, toluene, 5, 9, 14, 25, 26, 30, 64, 89, 111, 113, 117,
450, 452 119, 120, 122, 124, 126, 128, 131, 132, 179, 182,
Superoxide, 536 185, 195, 197, 226, 252, 291, 315, 325, 327, 335,
suppliers, 372 336, 340, 377, 382, 402, 525
supramolecular, 543 tones, 235
Supramolecular gels, xii, 173, 176, 177, 203, 205 topology, 281, 356
surface area, 12, 27, 177, 198, 379 toxic waste, 214, 532
surfactant, 5, 22, 25, 27, 216, 223, 224, 244 toxicity, 212, 368, 369, 422, 457, 461, 477, 509
surfactants, 525, 535 toxicology, 212
sustainability, 258, 366, 408 traits, 509
Suzuki coupling reaction, xiii, 234, 238, 239, 240, transesterification, xiii, 209, 214, 217, 228
241, 242, 260 transfer, 522, 527, 534, 535, 536
swelling, 318 transformation degrees, 539
symmetry, 150, 285, 319, 526 transformation product, 530, 543
synergistic, 546 transformations, xv, 49, 69, 210, 213, 216, 219, 234,
237, 258, 280, 366, 368, 371, 372, 389, 437, 456,
T 457, 551
transition, 522, 523, 526, 527, 536, 544, 554
Taiwan, 365
transition metal, ix, x, xi, xiii, xvii, 1, 49, 107, 108,
tantalum, 5
109, 110, 116, 138, 140, 155, 158, 209, 211, 221,
tar, 7
228, 234, 235, 237, 259, 266, 282, 356, 428, 455,
target, xvii, 160, 163, 455, 461, 502, 521
456, 464, 496, 502, 522, 526, 536
TCE, 534
transition temperature, 3
technological advances, 158
transmission, 371, 440
technologies, 234, 408, 436
transport, 177, 348
technology, xv, 365, 367, 372, 389, 408
transportation, 436
telephone, 1
Index 513
trifluoroacetate, 9, 350 volatility, 210

trifluoroacetic acid, 20, 493
triggers, 176
W
triglycerides, 213
Washington, 98, 229, 411
triphenylphosphine, 250
waste, 49, 210, 227, 366, 367, 450, 451
tryptophan, 528
wastewater, 437
tumor cells, 509
water, 15, 28, 83, 91, 93, 151, 179, 195, 197, 203,
tungsten, 3, 5, 49, 398
204, 211, 214, 216, 217, 218, 221, 222, 224, 226,
turnover, 16, 19, 93, 167, 193, 198, 290, 311, 313,
235, 244, 251, 254, 260, 267, 293, 303, 367, 374,
317, 347, 356, 462, 463, 466, 467, 468, 469, 471,
376, 389, 419, 422, 423, 437, 451, 467, 468, 535
472, 474, 494, 498
wavelengths, 372
twist, 31
weak interaction, 189
U wires, 203
wood, 444, 450, 452
ultrasonic frequency, 375, 406, 408 workers, 9, 14, 20, 23, 52, 75, 76, 78, 80, 81, 108,
ultrasound, xv, 12, 366, 371, 372, 375, 376, 378, 150, 152, 157, 160, 163, 250, 251, 258, 296, 319,
397, 400, 401, 404, 405, 407 331, 339
uniform, 6, 437 worldwide, 235
universe, 366
urea, 49, 69, 82, 175
X
urease, 536
X-ray analysis, 155, 187
UV irradiation, 27
X-ray diffraction, 175, 176, 285
UV radiation, 89
xylene, 535
V
Y
vacuum, 24, 176, 267, 268, 438, 439
yeast, 216
valence, 50, 155
yield, xi, xii, 5, 9, 14, 53, 56, 61, 62, 74, 79, 82, 83,
validation, 165
91, 112, 114, 121, 134, 136, 140, 143, 144, 178,
values, 545, 550, 551, 560
185, 198, 211, 216, 218, 219, 236, 237, 238, 239,
vanadium, 3, 108, 109, 125, 127, 128, 129, 130, 137,
241, 243, 244, 251, 255, 269, 282, 321, 324, 329,
140, 266
335, 337, 344, 346, 350, 354, 355, 381, 383, 385,
vancomycin, 205
389, 396, 397, 404, 405, 458, 468, 476, 486, 498,
vapor, 4, 30, 211, 212, 214
522, 561
variables, 14
yttrium, 4
variations, 407, 466, 468
velocity, 65 Z
versatility, 215, 456
vibration, 446 zeolites, 10, 177, 523
viscosity, 179, 212, 243, 280, 283, 287, 438, 439, zinc, 158, 320, 323, 426, 451
451 zirconia, 4
vision, 436 zirconium, 4

Homogeneous Catalysts Types Reactions and Applications

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CHEMICAL ENGINEERING METHODS AND TECHNOLOGY

Additional books in this series can be found on Nova’s website

Additional E-books in this series can be found on Nova’s website

HOMOG OUS CATALY

NOTICE TO THE READER

LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA

Homogeneous catalysts : types, reactions, and applications / editor, Andrew

Published by Nova Science Publishers, Inc. © New York

Chapter 10 Recent Strategies in Phase Transfer Catalysis and its Application

In chemistry, homogeneous catalysis is a sequence of reactions that involve a catalyst in

ammoxidation of propene to acrylonitrile, olefin epoxidation (ARCO and Halcon processes),

toxic, glycerol is a biodegradable, recyclable liquid that is manufactured from renewable

used as an intermediate in the fabrication of pharmaceuticals. The oxovanadium (IV) complex

METALLIC NANOPARTICLES NANOCOMPOSITES:

Rocío Redón*, N. G. García-Peña and F. Ramírez-Crescencio

= Metallic NPs Intra-molecular interactions

Sahoo and coworkers [55] have obtained tungsten nanoparticles by thermal

tetrahedral nanoparticles over anthracene, with up to 99.3% selectivity for 1,2,3,4,5,6,7,8-

were tested in the catalytic hydrogenation of cyclohexene to cyclohexane, styrene to

tested in the selective hydrogenation of dehydrolinalool (3,7-dimethyloct-6-ene-1-yne-3-ol,

hydrogenation or the selectivity. Nanospheres derived from hydroxylated polyisoprene (PHI),

catalytic oxidation of several 1,2-diols to α–hydroxy-carboxylates with gold nanocolloids

CONCLUDING REMARKS AND FUTURE PROSPECTS

ABOUT THE AUTH

[11] S. Desportes, D. Steinmetz, M. Hemati, K. Philippot, B. Chaudret, Powder Technol.

[63] W. Tu, B. Denizot, J. Colloid Interf. Sci. 310 2007 167–170.

[86] D. Chakravorty, S. Basu, B. N. Pal, P. K. Mukherjee, B. Ghosh, K. Chatterjee, A. Bose,

[115] N. A. Dhas, C. P. Raj, A. Gedanken. Chem. Mat. 10 1998 1446-1452.

[170] I. Balint, A. Miyazaki, K. Aika. J. Catal. 220 2003 74-83.

[200] M. A. Gelesky, S. S. X. Chiaro, F. A. Pavan, J. H. Z. dos Santos, J. Dupont. Dalton

[300] Z. Yinghuai, K. Chenyan, A. T. Peng, A. Emi, W. Monalisa, L. K.-J. Louis, N. S.

RECENT EVOLUTION OF OXIDATION CATALYSIS

Carla D. Nunes* and Pedro D. Vaz

chemistry of MoVI has stimulated considerable interest in view of its biochemical

of useful materials such as dyes, pharmaceuticals, perfumes and plastics [47,48]. As a

Ethylbenzene Cumyl Trityl

OXIDATIONS WITH [MOVIO2]2+ COMPLEXES AS CATALYSTS

Table 1. Catalytic performances of catalysts based on MoO2X2L complexes (X = Cl, Br,

tbhp 73 100 122

tbhp 100 100

F H2O2 99 100 123

Cl tbhp 100 100 124

H2O2 68 100 125

tbhp 100 100 126

H2O2 80 100 127

tbhp 96 100 128

Table 3. Catalytic performance of MoO2R2(Me-p-tolyl-dab)2 (R = Cl, CH3) complexes

R Solvent / RTIL Conversion % Epoxide sel. %

In 1999 Bellemin-Caponnaz and others demonstrated this by applying the ligand 2-

tbhp 92 100 <5 147

Table 6 evidences the most relevant achievements stressing catalysts capability to

OXIDATIONS WITH [MOVIO(O2)2]2+ COMPLEXES AS CATALYSTS

Ligand Olefin Oxidant Epoxide Yield % ee %

Sulfide Reaction time / h Yield / % ee (%), config

Scheme 4. Kinetic resolution of sulfoxides during sulfoxide to sulfone oxidation.

In oxoperoxo chemistry of Mo, an important structural motif, in which two peroxo

Table 7. Epoxidation of hept-1-ene with MoO(O2)2L (L = P ligands in Chart 15)

Shortly after, Yoon and co-workers reported the preparation of MoVI-oxodiperoxo

Table 8. Aromatic olefin epoxidation using 2-(1-pyrazole)pyridineoxodiperoxo MoVI

n.d. = not determined, due to small yield of epoxide.

Table 9. Catalytic oxidation of olefins, alcohols, amines and sulfides using

Substrate Product Temp. / K Yield

OXIDATIONS WITH [MOII(CO)2,3]2+ COMPLEXES AS PRE-CATALYSTS