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Organophosphorus Chemistry

Volume 45
A Specialist Periodical Report

Organophosphorus Chemistry
Volume 45

A Review of the Literature Published between

January 2014 and January 2015

Editors
D. W. Allen, Sheffield Hallam University, Sheffield, UK
J. C. Tebby, Staffordshire University, Stoke-on-Trent, UK
D. Loakes, Laboratory of Molecular Biology, Cambridge, UK

Authors
Piotr Bałczewski, Polish Academy of Sciences, Łódź, Poland and Jan
Długosz University in Cze ˛stochowa, Poland
Agnieszka Bodzioch, Polish Academy of Sciences, Łódź, Poland
Goutam Brahmachari, Visva-Bharati, Santiniketan, India
Mário J. F. Calvete, University of Coimbra, Portugal
Rui M. B. Carrilho, University of Coimbra, Portugal
Vadapalli Chandrasekhar, Indian Institute of Technology, Kanpur, India
Piotr Guga, Polish Academy of Sciences, Łódź, Poland
G. Keglevich, Budapest University of Technology and Economics,
Hungary
Anna D. Maciaszek, Polish Academy of Sciences, Łódź, Poland
Ramakirushnan Suriya Narayanan, National Institute of Science Education
and Research, Bhubaneswar
Marco Noè, Ca’ Foscari University of Venice, Italy
Romana Pajkert, Jacobs University, Bremen, Germany
Mariette M. Pereira, University of Coimbra, Portugal
Alvise Perosa, Ca’ Foscari University of Venice, Italy
Gerd-Volker Röschenthaler, Jacobs University, Bremen, Germany
Maurizio Selva, Ca’ Foscari University of Venice, Italy
ISBN: 978-1-78262-433-2
PDF eISBN: 978-1-78262-693-0
EPUB eISBN: 978-1-78262-822-4
ISSN: 0306-0713
DOI: 10.1039/9781782626930

A catalogue record for this book is available from the British Library

r The Royal Society of Chemistry 2016

All rights reserved

Apart from fair dealing for the purposes of research for non-commercial
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Preface
David Allen,a David Loakesb and John Tebbyc
DOI: 10.1039/9781782626930-FP005

This volume, No. 45 in the series, (first published in 1970 under the
editorship of Professsor Stuart Trippett), covers the literature of or-
ganophosphorus chemistry published in the period from January 2014 to
January 2015, and continues our efforts to provide an up-to-date survey of
progress in this topic which continues to generate a vast amount of re-
search. Unfortunately, for this volume, we have been unable to secure
coverage of the oligo- and poly-nucleotides area and would welcome
approaches from prospective authors who might consider taking on this
chapter in future volumes. In addition, we have again been unable to
secure coverage in this volume of the application of physical methods in
organophosphorus chemistry. On a brighter note, we welcome to our
team of authors Professor Goutam Brahmachari, who has contributed a
guest chapter reviewing recent progress in green and energy-efficient
synthetic approaches in organophosphorus chemistry and Prof. V.
Chandrasekhar and Dr R. Suriya Narayanan who have reviewed the wide
ranging phosphazene area. The continuing vitality of research in phos-
phorus chemistry was again demonstrated at the 20th International
Conference on Phosphorus Chemistry, held in Dublin, Ireland from 28th
June–2nd of July 2014, and papers from this have now been published in
a special edition of Phosphorus, Sulfur Silicon Relat. Elem., 2015, 190 (5–6).
We also note the publication of a whole issue (2014, No. 10) of the Eur. J.
Inorg. Chem., edited by Maria Caporali, which is devoted to a wide range
of papers on advances in the chemistry of phosphorus, and a special
edition (2014, No. 7–8) of Phosphorus, Sulfur Silicon Relat. Elem., edited by
Geörgy Keglevich, Konstantin Karaghiosoff and Martin Rudd, celebrating
the 86th birthday of Louis D. Quin.
The use of a wide range of tervalent phosphorus ligands in homo-
geneous catalysis has again continued to be a major driver in the
chemistry of both traditional P–C-bonded phosphines and also that of
tervalent phosphorus acid derivatives. The application of tertiary phos-
phines and related compounds as nucleophilic catalysts in the reactions
of electrophilic unsaturated systems involved in new synthetic ap-
proaches has also continued to grow. The reactions of sterically-crowded
arylphosphine-arylboranes (Frustrated Lewis Pair (FLP) systems) in the
activation of small molecules such as dihydrogen and carbon dioxide has
shown further development and now extends to an increasing number of
papers on phosphine adducts of other Lewis acids, notably alanes.
a
Biomedical Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UK
b
Medical Research Council, Laboratory of Molecular Biology, Hills Road,
Cambridge CB2 0QH, UK
c
Division of Chemistry, Faculty of Sciences, Staffordshire University, Stoke-on-Trent
ST4 2DE, UK

Organophosphorus Chem., 2016, 45, v–viii | v


c The Royal Society of Chemistry 2016
Whereas long-established topics such as the chemistry of diphosphenes
and phosphaalkynes have again received comparatively little study, the
chemistry of phosphaalkenes (and related P¼C¼X compounds), and the
less-developed groups of low coordination number phosphorus com-
pounds, in particular phosphenium ions, phosphinidenes, and their
complexes with carbenes and metal ions, has again dominated the area.
In phosphine chalcogenide chemistry, interest in the development of
methods for their synthesis, and their applications as new components in
opto-electronic devices, has again shown considerable growth. Notable
again are efforts to develop catalytic versions of key reactions, e.g., the
Wittig, Appel and Mitsunobu reactions, in which the key phosphine re-
agent is regenerated by in situ reduction of the generated phosphine
oxide. The chemistry of phosphonium salts and related ylides has again
shown remarkable activity, with particular reference to catalytic appli-
cations and, in particular, to the synthesis and applications of phos-
phonium salts as ionic liquids that display higher thermal and
electrochemical stabilities compared to related ammonium salts and also
have potential as new solvents in organic synthesis and as stabilisers for
nanoparticle systems.
For this volume there is no chapter on oligonucleotides whilst we seek
new authors (anyone interested in contributing to this chapter should
contact one of the editors). We welcome a new team for the mono-
nucleotide chapter of Piotr Guga and Anna Maciaszek. Nucleoside
phosphates and polyphosphates, as well as their cyclic congeners and
covalent adducts, all play important roles in all living systems. Probably
adenosine triphosphate (ATP), adenosine 3 0 ,5 0 -cyclic phosphate (cAMP)
and S-adenosylomethionine (SAM) are the most widely known examples
of the main biophosphate families. For many years, chemists and bio-
chemists understood nucleoside biophosphates to be esters of phos-
phoric, diphosphoric or triphosphoric acids, with only a small margin
left for phosphonates. This family soon grew acquiring derivatives of up
to heptaphosphoric acids, e.g., regulatory symmetrical P1,P7-di(adeno-
sine-5 0 )-heptaphosphate (or AP7A) operating with the P2Y subfamily of
G-protein coupled receptors on cell surface in mammalian tissues.
Phosphorothioate analogues of DNA were then discovered and their
enzymatic hydrolysis produces nucleoside phosphorothioates as well as
enzymes that would convert them to nucleoside 5 0 -phosphates. These are
now routinely used not only for biochemical mechanistic studies but also
as potential drugs or prodrugs with anticancer or antiviral activity,
exerted by, e.g., inhibition of enzymes vital for fast-proliferating cells or
for virus replication. The chapter on mononucleotides summarises the
achievements reported for a broad range of modified nucleoside mono-
to poly-nucleotide analogues, covering both synthesis and biochemical
activities.
The chapter on quinquevalent phosphorus acids and their derivatives
continues to be an area of interest. It shows some of the most important
achievements in the area of organophosphorus compounds containing
three P–O bonds (phosphates), two P–O and one P–C bonds (phospho-
nates) as well as one P–O and two P–C bonds (phosphinates), in addition

vi | Organophosphorus Chem., 2016, 45, v–viii

to one phosphoryl P¼O bond. Each section covers synthesis, reactions
and biological applications. New subsections covering miscellaneous
applications of phosphoric, phosphonic and phosphinic acids and their
derivatives, other than biological ones, have been added in this volume.
In the review period, most syntheses of phosphonic acids and their de-
rivatives involved simple organophosphorus reagents, like dialkyl and
trialkyl phosphites that were widely used in reactions with alkynes and
alkenes to obtain alkenyl and alkynylphosphonates as well as with imi-
nes, ketimines, ketones, aldehydes and nitriles to afford imino- and
aminophosphonates, and hydroxyphosphonates.
In the field of five and six coordination phosphorus chemistry, most of
the progress has been in revealing reaction mechanisms and especially
their role as intermediates in determining the stereochemical outcomes
of reactions. This has been particularly rewarding in biological fields
such as the mechanism of selective transfer of phosphorus groups as well
as DNA cleavage. It has also been shown that the presence of the hydroxyl
group in the 2 0 position of ribose in RNA facilitates many transformations
in the absence of enzymes by the intervention of intermediates such as
cyclic phosphates. Other notable research includes intramolecular N–H
bond cleavage of amines by oxidative addition to tricoordinate phos-
phorus compounds. The reaction proceeds smoothly under mild con-
ditions to give structurally robust phosphorane adducts. The chemistry of
hexacoordinated compounds has been mainly limited to the synthesis
and modification of diverse perfluoroalkyl fluorophosphates. A number
of theoretical studies have also given valuable information in a
variety areas.
Phosphazenes continue to be widely studied. Acyclic phosphazenes
include various types of iminophosphoranes, dimeric analogues, and
various types of cyclophosphazenes, polyphosphazenes and hybrid
polymers. The potential applications of these compounds are discussed.
Highlights of the research include the preparation of bisphosphazene
super bases that can act as ‘‘proton sponges’’, a chiral diphosphazene
copper complex that catalyses cyclopropanation, and click reactions. The
bulk of phosphazene research continues to be on the cyclic systems. This
includes some new members of the rare 4-membered cyclophosphazenes
and the isolation of P5–P9 chlorocyclophosphazenes. Fluorescent den-
drimer-like structures have been made from halogenocyclophos-
phazenes, and a Fe31 concentration of 4.8 mM was detected using an
azidocyclophosphazene coupled to a rhodamine dye. Cyclophosphazene
dendrimers, hexa- and dodeca-porphyrin derivatives and viologen-
containing complexes with pseudorotaxanes have been made. A hexa-
substituted cyclophosphazene is a plasticizer for starch. Dendrimeric
cyclophosphazenes were evaluated as flame retardants and combined
with graphite to make anodes for lithium batteries. Composites with
montmorillonite are very good flame retardants and a thermally stable
tris-spiro phosphazene was used to prepare flame-retardant viscose
fibres. An abundance of new applications for cyclophosphazene-based
ligands includes encapsulating cobalt nanoparticles and reactions with
diiron- and dimolybdenum-carbonyls. Rigid bulky co-substituents on

Organophosphorus Chem., 2016, 45, v–viii | vii

polyphosphazenes have given elastomers. Hydrophobic ethoxypho-
sphazenes are a new class of bio-erodible polymers. Advances in drug
delivery include the use of biodegradable microspheres and hollow
structures. Dehydration of fructose into 5-hydroxymethylfurfural was
achieved by homogeneous catalysis involving phosphazenes. Fluorinated
phosphazenes have been shown to improve the thermal and safety
performance of lithium-ion battery electrolytes and also to make
luminescent ionic liquids. A polymeric fluorinated cyclophosphazene
improved the interfacial properties of carbon fibre composites.

viii | Organophosphorus Chem., 2016, 45, v–viii

CONTENTS

Cover
A selection of organophosphorus
molecules. Image reproduced by
permission of Dr David Loakes.

Preface v
David Allen, David Loakes and John Tebby

Phosphines and related C–P bonded compounds 1

D. W. Allen
1 Introduction 1
2 Phosphines 1
3 pp-Bonded phosphorus compounds 26
4 Phosphirenes, phospholes and phosphinines 30
References 35

Tervalent phosphorus acid derivatives 51

Mariette M. Pereira, Rui M. B. Carrilho and
Mário J. F. Calvete
1 Introduction 51
2 Halogenophosphorus compounds 51
3 Tervalent phosphorus amides 54
4 Tervalent phosphorus esters 70
References 94

Organophosphorus Chem., 2016, 45, ix–xi | ix


c The Royal Society of Chemistry 2016
Phosphine chalcogenides 99
G. Keglevich
References 128

Phosphonium salts and P-ylides 132

Maurizio Selva, Alvise Perosa and Marco Noè
1 Introduction 132
2 Phosphonium salts 132
3 Phosphonium-based ionic liquids (PILs) 143
4 P-ylides (phosphoranes) 152
References 158

Nucleotides and nucleic acids: mononucleotides 170

Piotr Guga and Anna D. Maciaszek
1 Introduction 170
2 Nucleoside mono-, di- and triphosphates 170
3 Nucleoside phosphonates 182
4 Nucleotide prodrugs 185
5 Analogues of mRNA caps 189
6 Fluorescently labelled probes 191
References 192

Quinquevalent phosphorus acids 196

Piotr Ba!czewski and Agnieszka Bodzioch
1 Introduction 196
2 Phosphoric acids and their derivatives 197
3 Phosphonic acids and their derivatives 264
4 Phosphinic acids and their derivatives 335
References 345

Pentacoordinated and hexacoordinated compounds 354

Romana Pajkert and Gerd-Volker Röschenthaler
1 Introduction 354
2 Pentacoordinated phosphorus compounds 354
3 Hexacoordinated compounds 366
References 374

x | Organophosphorus Chem., 2016, 45, ix–xi

Phosphazenes 375
Vadapalli Chandrasekhar and Ramakirushnan Suriya Narayanan
1 Introduction 375
2 Acyclic phosphazenes 375
3 Cyclophosphazenes 386
4 Polyphosphazenes 417
5 Hybrid systems 422
6 Applications 427
Acknowledgements 433
References 433

Green synthetic approaches in organophosphorus chemistry: 438

recent developments with energy-efficient protocols
Goutam Brahmachari
1 Introduction 438
2 Recent advances in the development of energy-efficient 439
protocols in organophosphorus chemistry
3 Conclusions 484
Acknowledgements 484
References 484

Organophosphorus Chem., 2016, 45, ix–xi | xi

Abbreviations
BAD Benzamide adenine dinucleotide
cDPG Cyclodiphospho D-glycerate
CE Capillary electrophoresis
CK Creatine kinase
CPE Controlled potential electrolysis
Cpmp 1-(2-chlorophenyl)-4-methoxylpiperidin-2-yl
CV Cyclic voltammetry
DETPA Di(2-ethylhexyl)thiophosphoric acid
DMAD Dimethylacetylene dicarboxylate
DMF Dimethylformamide
DMPC Dimyristoylphosphatidylcholine
DRAMA Dipolar restoration at the magic angle
DSC Differential scanning calorimetry
DTA Differential thermal analysis
ERMS Energy resolved mass spectrometry
ESI-MS Electrospray ionization mass spectrometry
EXAFS Extended X-ray absorption fine structure
FAB Fast atom bombardment
Fpmp 1-(2-fluorophenyl)-4-methoxylpiperidin-2-yl
HPLC High-performance liquid chromatography
LA-FTICR Laser ablation Fourier Transform ion cyclotron resonance
MALDI Matrix assisted laser desorption ionization
MCE Micellar electrokinetic chromatography
MIKE Mass-analysed ion kinetic energy
PAH Polycyclic aromatic hydrocarbons
QDA Hydroquinone-O,O 0 -diacetic acid
PMEA 9-[2-(phosphonomethoxy)ethyl] adenine
SATE S-acyl-2-thioethyl
SIMS Secondary ion mass spectrometry
SSAT Spermidine/spermine-N1-acetyltransferase
SSIMS Static secondary ion mass spectrometry
TAD Thiazole-4-carboxamide adenine dinucleotide
tBDMS tert-Butyldimethylsilyl
TFA Trifluoroacetic acid
TGA Thermogravimetric analysis
TLC Thin-layer chromatography
TOF Time of flight
XANES X-ray absorption near edge spectroscopy

xii | Organophosphorus Chem., 2016, 45, xii–xii


c The Royal Society of Chemistry 2016
Phosphines and related C–P bonded
compounds
D. W. Allen
DOI: 10.1039/9781782626930-00001

1 Introduction
This chapter covers the literature published during 2014 relating to the
above area. The number of papers published in 2014 is similar to that in
2013 and again it has been necessary to continue to be selective in the
choice of publications cited. Nevertheless, it is hoped that the most
significant developments have been noted. The past year has again seen
the publication of a considerable number of review articles and many of
these are cited in the various sections of this report. The use of a wide
range of tervalent phosphorus ligands in catalysis continues to be a
major driver in the chemistry of traditional P–C-bonded phosphines
(and also that of tervalent phosphorus acid derivatives, covered in
detail elsewhere in this volume). As in recent years, a noteworthy feature
of the literature reviewed here is the large number of papers reporting
studies of the reactivity of phosphines, in particular those involving
nucleophilic attack at a carbon atom of an electrophilic substrate. Re-
cent general reviews of organophosphorus chemistry relevant to the
catalysis area have provided coverage of developments in the application
of chelating P,N-donor ligands,1,2 and applications of the electron-
deficient diphosphine DIFLUORPHOS3 and P(III)-functionalised calix-
arenes and resorcinarenes.4 Other more general reviews include a survey
of methods for the synthesis of phosphines involving C–P bond
formation,5 asymmetric catalysis as a method for the synthesis
of chiral organophosphorus compounds,6 the synthesis and appli-
cations of a-cationic phosphines,7 the synthesis, reactivity and co-
ordination chemistry of secondary phosphines8 and the coordination
chemistry of main group elements with phosphine, arsine and stibine
ligands.9

2 Phosphines
2.1 Preparation
2.1.1 From halogenophosphines and organometallic reagents. This
route has continued to be applied widely, with most work involving the
use of organolithium reagents. Although very few reports of Grignard
and related organomagnesium-based procedures have appeared, these
reagents have found use, in combination with chlorophosphines, in the

Biomedical Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UK.

E-mail: D.W.Allen@shu.ac.uk

Organophosphorus Chem., 2016, 45, 1–50 | 1


c The Royal Society of Chemistry 2016
development of routes to the diphosphine (1) and related chelating
phosphino-phosphite ligands,10 and, in a copper(I) chloride-catalysed
procedure, to the sterically crowded (ter-aryl)monophosphine (2).11 New
sterically-crowded phosphines, e.g., (3)12 and (4),13 have also been
prepared using arylithium–chlorophosphine routes. The latter approach
has also been applied to the synthesis of a wide range of carbon-
functionalised tertiary phosphines, including diphosphinoaryloxadia-
zoles, e.g., (5),14 a series of wide-bite-angle phosphinoaryl-cyclophosphite
ligands, e.g., (6),15 and phosphines bearing a pyridinium betaine
substituent (7),16 sulfonate and diethylphosphonato groups, (8),17 the
highly fluorescent Bodipy chromophore (9),18 the chiral, cyclopropane-
bridged phosphino-oxazoline system (10),19 chiral o-sulfonamidoaryl
phosphines,20 and further examples of chiral, unsymmetrical bisphos-
phino[2.2]-paracyclophanes.21 Also reported is a range of phosphines
bearing hydroxyl- or ether-functionalities, including tris(2-isopropoxy-
phenyl)phosphine,22 further resorcinarenyl-phosphines and their oxides,23
and the multi-stereogenic chiral phosphines (11).24 Among new hetero-
cyclic phosphines obtained using the organolithium-chlorophosphine
approach is a series of chiral dibenzophosphepines, e.g., (12).25 The syn-
thesis of heteroarylphosphines, in which a phosphino group is attached
directly to the heterocyclic ring, has also continued to attract attention,
recent examples including new 2-thienyl- and 2,2 0 -bithienyl-di(isopropyl)-
phosphines, e.g., (13),26 the phosphinopyrroles (14),27 the phosphino-
imidazoles (15),28 and the anionic benzimidazolylphosphine (16).29
Arylithium- (or Grignard)-chlorophosphine routes also continue to be
used in the synthesis of phosphino-functional metallocenes. Interesting
examples include a library of planar-chiral phosphino-alkenyl chromium
ligands, e.g., (17),30 phosphinometallocenes containing rhenium,31
ruthenium, osmium, iron and cobalt,32 and further phosphinoferrocenes,
e.g., the boron-appended bis(diphenylphosphino)ferrocene (18),33 and a
series of new chiral 1-alkylamino-2-diorganophosphinoferrocenes.34

But But
P(C6F5)2 PAr2
PCy2

Pri Pri
P(C6F5)2
Ph
Br
Pri

(1) (2) (3) Ar = 2,4,6-Pri3C6H2

R R
X X
O
O
R P R Ph2P P
Ph2P N N PPh2
But O O

(4) R = H, Me, OMe, Pri, But, or CF3; (5) (6)

X = H, OMe or NMe2

2 | Organophosphorus Chem., 2016, 45, 1–50

 PR12

P(O)(OEt)2
H Ar
PPh2 P

PriN NPri
SO3
N N
O O B
R 2 R2
(7) (8) Ar = Ph or 4-ButC6H4 (9) R1 = Cy or Ph; R2 = Me or Ph
PPh2
R
OH
But2P N OH P But
R
O
Ph

(10) (11) R = H, o-Me or m-Me (12) R = e.g., C6H11CH2, PhCH2,

MesCH2 or 2-NaphthylCH2

PPri2 PR2 R12P N N

S S N
NMe2 PR22

(13)
(14) R = Ph, o-Tol or But (15) R1 = But, R2 = Ph
R1 = Ph, R2 = But

N
Ph2P Ph2B
PPh2
N
Ph2P P
But
P Cr(CO)2
BPh3 Li Ph Ph Fe

(16)
(17) (18)

2.1.2 From metallated phosphines. Alkali metal-organophosphide

reagents, sometimes as borane-protected systems, remain the most
commonly used in the synthesis of new phosphines, the borane group
also providing protection against oxidation of the new phosphine dur-
ing purification steps. New phosphines reported using lithiophosphide
reagents in traditional procedures involving nucleophilic displacement
reactions of alkyl and aryl halides or sulfate esters include the phosphi-
nopyrimidines (19),35 the chiral, bicyclic phosphinoalkylpyridines
(20),36 and a range of chiral aminoalkylphosphines, e.g., (21).37 There
has also been considerable interest in the synthesis of phosphino-
silanes and phosphinoalkylsilanes via treatment of lithiophosphide

Organophosphorus Chem., 2016, 45, 1–50 | 3

reagents with chlorosilanes or chloroalkylsilanes. Among new systems re-
ported are the diphosphine (22) and the cyclic diphosphinotetrasilane
(23),38 the stable bicyclic diphosphasilirane (24),39 and the diphosphine
(25, R ¼ Me3Si), which, on treatment with chlorodiphenylphosphine
gives the tetraphosphine (25, R ¼ Ph2P).40 Ring-opening of small,
strained rings with metallophosphide reagents has afforded routes to
phosphine-tethered cyclopentadienyl chelate metallocene systems, e.g.,
(26), from the ring-opening of spiro[2,4]hepta-4,6-diene,41 new P-chiral
1,3-oxaphospholanes (27)42 and chiral 1,2- and 1,3-phosphinoalcohols43
from optically pure epoxides and oxetanes. Generation of new lithio-
phosphide reagents via lithium-promoted cleavage of P–P bonds has
enabled routes to the bicyclic tetraphosphine (28) via the activation
of white phosphorus using sterically crowded arylithium reagents
in the presence of B(C6F5)3,44 and to o-dicarbaborane-fused-1,2,3-
triphospholanes and related-1-aza-2,5-diphospholanes, from related
o-dicarbaborane-1,2-diphosphetanes.45 Both lithium- and potassium-
diorganophosphide reagents have been used (together with other
approaches) for the synthesis of phosphines bearing N-heterocyclic
boranyl substituents, e.g., (29),46 and a route to benzazaphospholine-2-
carboxylic acids (30) is provided by metalation of N-methyl- and N-
neopentyl-o-phosphinoanilines using sodium, followed by alkylation at
phosphorus and cyclisation with glyoxylic acid hydrate.47 Potassioorgano-
phosphide reagents have also been used in routes to new chiral phosphino-
alkylamines, e.g., (31), subsequently used in the synthesis of chiral ligands
of the type Cy2PCH2CH¼NCH(R)CH2PPh2,48 the diphosphines (32),49 the
1,3,5-triazenyltriphosphine (33),50 and the tetraphosphine (34).51
H3B
PAr2

N N N Ph N PPh2

Ph2P R
n X
n
t
(19) R = Ph2P or Bu (20) n = 1 or 2; Ar = Ph or o-Tol (21) X = CH2; n = 0 or 1
X = O; n = 1

O
H Me2 Me2Si SiMe2 Pri2Si SiPri2
P Si Hyp Hyp P P Hyp P P
Hyp Si P Me2Si SiMe2 Si
Me2 H i
Pr 2

(22) Hyp = tris(trimethylsilyl)silyl (23) (24)

PHBut
O
R P P R Fe
Ph Ph P
t
But BH3
Bu HP

(25) (26) (27)

4 | Organophosphorus Chem., 2016, 45, 1–50

 Interest in the synthesis and structural characterisation of metallo-
phosphide reagents has also continued. The sterically-crowded lithio-
phosphide LiP(SiMe3)PBut2 has been obtained by the reaction of the
P,P-diphosphine (Me3Si)2P–PBut2 with n-butyllithium (in various solvents)
and fully characterised by crystallography and multinuclear NMR spec-
troscopy.52 Recent work by the Goicoechea group on the characterisation
and reactivity of the [HP7]2 ion has now been extended to include the
related arsenic anion [HAs7]2, and studies of the reactions of both
anions with heteroallenes to form new amide-functional cluster anions.53
A series of pincer calcium, magnesium and zinc bis(o-diphenylphos-
phinoaryl)phosphides has been prepared by metallation of the related
secondary bis(o-phosphinoaryl)phosphine and used as catalysts for the
ring-opening polymerisation of e-caprolactone.54 The stannylphosphide
reagent Na[P(SnPh3)2], together with the Zintl salt Na3[P7], are formed in
the reaction of P4 with in situ-generated Na[SnPh3]. The bis(triphenyl-
stannyl)phosphide reagent has been used to prepare related indium,
tin and gold triphenylstannylphosphides and the Zintl salt to prepare
the stannylheptaphosphide P7(SnPh3)3 and the related trimethylsilyl
system.55 A sterically-crowded tin(II) phosphanide has also been charac-
terised.56 The applications of stannylphosphines in the synthesis of new
phosphines, arsines and stibines are included in a recent review.57 Also
reviewed is the chemistry of rare earth complexes of anionic phosphorus-
containing ligands, including organophosphides and dianionic phos-
phinidenes (RP2).58 Some iridium diorganophosphide systems have also
been characterised.59

R2
Dipp
P N P
DmpP PMe B PR1R2 COOH
P N N
Dipp R1
(28) (29) R1 = R2 = H or Ph (30) R1 = Me, R2 = Pri
1 2
R = H, R = Ph R1, R2 = neopentyl
PPh2

ArHP PHAr
R PPh2
N N
H2N
N

Ph2P PPh2
i
(31) R = Ph, CH2Ph or Pr (32) Ar = Tripp or Mes (33)
Ph2P PPh2

PR2
N PMe2
P Me Si
R
PMe2

PPh2 PPh2

(34) (35) R = alkyl or aryl (36) R = Ph or Pri

Organophosphorus Chem., 2016, 45, 1–50 | 5

 The use in synthesis of phosphine reagents metallated at atoms other
than phosphorus has again continued to attract interest and a few further
applications have been described. The usual starting point is a phos-
phine metallated at a carbon atom that is the site of subsequent trans-
formations. Recent applications of C-lithiated phosphines include
further work on the synthesis of the modular C1-symmetric chiral P,N
ligands (35),60 and also on the C-lithiation of methylphosphines, pro-
viding routes to tripod phosphine ligands, e.g., (36),61 and (37),62 and the
unusual chiral, chelating anionic bis(phospholane) ligand (38).63 Interest
has also continued in the structural characterisation of C-metalated
phosphines. Two groups have reported studies of the synthesis and
stability of metal salts derived from diphosphines and their borane
adducts e.g., (39).64,65 Further work has also appeared on the chemistry of
N-metallated phosphinoamide ligands.66

Ph P BH3
Ph
B M B Li(thf)2 R2P PR2
Ph
PAr2 P
Ar2P PAr2

(37) Ar = p-CF3C6H4 (38) i

(39) R = Ph or Pr

2.1.3 By the addition of P–H to unsaturated compounds. Addition

of P–H bonds to unsaturated compounds continues to be used under a
variety of conditions involving thermal-, radical (UV or AIBN)-, base-
or metal complex-catalysed initiation in the synthesis of a range of
new phosphines (and related chalcogenides). The use of borane-
protected primary and secondary phosphines in addition reactions
has also continued. AIBN-initiated addition of the diphosphine
PhP(H)(CH2)2P(H)Ph to an acrylamide has given a diastereoisomeric
mixture of the amide-functional diphosphine (40)67 and new tripodal
phosphines, e.g., (41), have been obtained by AIBN- (or uv)-inititiated
addition of secondary phosphines to trivinylethers of triols and amino-
triols, the additions proceeding in anti-Markownikov mode with good
chemo- and regio-selectivity.68 Nitrilium triflates, [RNCR]1 OTf, have
been shown to behave as imine synthons, readily undergoing addition
of primary phosphines at 78 1C, to give, after depronation, the phos-
phaamidines (42). The addition product derived from Mes*PH2, how-
ever, undergoes a [1,3] H-shift under the reaction conditions to form
the phosphaalkene (43).69 Similarly, secondary phosphine-boranes have
been shown to undergo base-promoted addition to carbodiimides to
form the phosphaguanidine-boranes (44), easily deprotected with
DABCO to give the free phosphines.70 Base-promoted addition of
phenylphosphine to an N-vinylbenzimidazole has given the tridentate
bis(benzimidazolyl)phosphine (45).71 The past year has, however, been
dominated by metal complex-catalysed procedures. Palladium complex-
catalysed procedures have been used widely in the synthesis of a range

6 | Organophosphorus Chem., 2016, 45, 1–50

of new phosphines. Examples include asymmetric 1,6-additions of
diarylphosphines to electron-deficient dienes bearing phosphonate or
sulfonate ester groups,72 and asymmetric additions to a range of ab-
unsaturated carbonyl compounds, e.g., chalcones,73,74 bg-unsaturated
a-ketoesters and amides,75 and N-enoylphthalimides.76 Also reported is
the development of a new chiral palladacycle, shown to catalyse the
asymmetric hydrophosphination of dimethyl acetylenedicarboxylate
with diphenylphosphine,77 and a palladium complex-catalysed formation
of P-stereogenic diarylphosphinites by addition of sterically-crowded
secondary diarylphosphines to the carbonyl group of p-benzoqui-
nones.78 Examples of catalysis using complexes of other, less expensive,
metals include an N-heterocyclic carbene–copper(I) complex-catalysed
asymmetric 1,4-addition of diarylphosphines to ab-unsaturated ke-
tones79 and a copper(II) acetate-catalysed hydrophosphination of styr-
enes in water at room temperature.80 Hydrophosphination of styrenes
(and other alkenes) has been achieved with the use of complexes of
ytterbium,81 zirconium82 and iron.83 Hydrophosphination of terminal
arylacetylenes has been achieved using a cyclopentadienyliron com-
plex.84 The pentamethylcyclopentadienyltin complex Cp*2SnCl2 has
been shown to catalyse the hydrophosphination of styrene, 2,3-
dimethylbutadiene and diphenylacetylene, providing the first example
of a p-block catalyst for hydrophosphination. This catalyst is also active
in promoting the dehydrocoupling of primary phosphines to give the
diphosphines RHP–PHR.85

Ph Ph
P P Ph
PR2 N
O
O O X
3 But PHR
i
PriHN NHPr

(40) (41) X = MeC, EtC or H2NC (42) R = Cy or Ph

Ph
Ph R2 N N P
NH N
Mes*
But P R1HN PR32 N

BH3 N

(43) (44) R1, R2 = Cy or Ph; R3 = Cy, But or aryl (45)

2.1.4 By the reduction of phosphine oxides and related compounds.

As in recent years, a wide range of reagents has been employed for the
reduction of phosphine oxides, usually at the end of a multistage syn-
thesis. Silane-based reagents continue to be widely employed and tri-
chlorosilane, usually in the presence of an amine base, has continued
to be the most commonly used in the final step of a multistage synthe-
sis. New phosphines prepared using this reagent in the absence of a
base include the 1-alkyl-3-phospholenes (46), in both racemic and
enantiopure forms,86 the hydroxyproline-derived bicyclic system (47),87
and the dicarboxybiphenylphosphine (48), from which a metal–organic

Organophosphorus Chem., 2016, 45, 1–50 | 7

framework (MOF) catalyst for C–C bond formation reactions was de-
veloped.88 Phosphines isolated following HSiCl3-R3N reduction of phos-
phine oxides include the chiral diphosphine (49),89 the 4,4 0 -dicarboxy-
functional 2,2 0 -BINAP system (50) (also a MOF precursor),90 new
BINAP-based dendritic diphosphine ligands,91 a series of 2-dialkylphos-
phino-1,1 0 -binaphthyls bearing bulky alkyl groups at phosphorus,92 the
chiral triptycene-based P,S-ligand (51),93 and a series of air-stable
P-chiral dihydrobenzoxaphosphole-oxazoline ligands, e.g., (52).94 Diphe-
nylsilane and phenylsilane have been used for phosphine oxide reduc-
tion in further work on the development of catalytic versions of Wittig
and related reactions,95,96 and in the first reported microwave-assisted
catalytic Wittig procedure.97 Keglevich and Kovács have reported a com-
parative case-study of the use of a range of silane reagents for the re-
duction of five-membered heterocyclic phosphine oxides. It was found
that while trichlorosilane and phenylsilane are efficient, they have
some disadvantages in terms of user-friendliness and cost, respectively.
In contrast, tetramethyldisiloxane (TMDS) and polymethylhydrosiloxane
(PMHS) are cheap and easier to use but are of lower reactivity. It was
concluded that the latter reagents could be used successfully at 110 1C
in toluene in the absence of any catalyst.98 A PMHS-Ti(OPri)4 combin-
ation has been used in further work on the synthesis of the diphosphi-
nobiferrocene-based Walphos analogues (53).99 Combination of TMDS
with Ti(OPri)4 has been applied in the development of a catalytic aza-
Wittig procedure100 and TMDS in combination with CuF2 in the isol-
ation of the fluorene-derived phosphine (54).101 Diethoxymethylsilane
in combination with bis(4-nitrophenyl)phosphate has been used for
phosphine oxide reduction in the development of a catalytic Appel-type
Ph3P-CCl4 approach to amide bond-formation from carboxylic acids
and amines.102 The first enantioselective catalytic Wittig reaction has
been developed, using trimethoxysilane for in situ phosphine oxide re-
duction.103 The Me3SiCl-LiAlH4 combination has been used for reduc-
tion of an arylphosphonate to the related primary phosphine in the
synthesis of an air stable, fluorescent primary phosphine analogue of
the Bodipy system (9).104 Other applications of aluminium hydride re-
agents include the use of LiAlH4 for the reduction of chlorophosphines
in the synthesis of di(2-thienyl)phosphine,105 the P–P-bridged polycyclic
diphosphine (55), (viewed as a diphosphorus-bisanthracene adduct and
subsequently shown to act as a reagent for the thermal transfer of the
P2 unit to 1,3-dienes to form new P–P-bridged polycyclic diphos-
phines,)106 and in a route to a related P–P-bridged diazapentalene sys-
tem.107 The NaAlH4-NaH combination was used in a new phosphine
oxide reduction protocol to reduce chorophosphonium chlorides,
formed by treatment of 1,2-bis(dialkylphosphino)ethane dioxides with
oxalyl chloride, to the related diphosphines.108 Dichloroalane, AlHCl2,
in tetraglyme was used in the synthesis of the primary phosphine (56)
from the related diethylphosphonate109 and DiBalH (Bui2AlH) was used
for phosphine oxide reduction in the synthesis of 2-dimethylphosphi-
nobiphenyl and 1,3-bis(diphenylphosphino)propane, as the final step

8 | Organophosphorus Chem., 2016, 45, 1–50

in an improved route to phosphines involving the direct conversion of
phosphonate esters to phosphine oxides using a Grignard-NaOTf
reagent.110 Other approaches for phosphine oxide reduction include
the use of magnesium for reduction of 1-dimesitylboryl-8-dichlorophos-
phinonaphthalene to give the first stable 1-phospha-2-boraacenaphthene
(57)111 and a combination of oxalyl chloride with the Hantzsch ester has
been shown to be an effective, metal-free reduction system for the reduc-
tion of tertiary phosphine oxides under mild conditions.112 Recent
examples of systems for the reduction of phosphine sulfides include the
use of Raney nickel in the synthesis of C-functionalised ferrocenyl-
phosphines bearing imidazolium113 and bulky aminoalkyl114 groups,
tris(dimethylamino)phosphine in the synthesis of new chiral C-alkoxy-
functionalised ferrocenylphosphines,115 and Schwartz’s reagent (Cp2ZrHCl)
in the synthesis of new diphosphinoalkyl-functional calix[4]arenes.116

HOOC

TsN
P
R P Ph2P
Ph COOH

(46) R = Et, Bui or Penti (47) (48)

PPh2
BuO N
N PPh2 PPh2
Ph2P

p-TolS
R

(49) (51)
(50) R = C C COOH

PR22
O
PR12 MeO2C
N R Fe
P
t MeO2C
Bu Fe
OMe
PPh2

(52) R = H, Ph or But (53) R1 = Ph, R2 = Ph or 3,5-(CF3)2C6H3 (54)

P Mes Mes
P B
P
PH2

(55) (56) (57)

Organophosphorus Chem., 2016, 45, 1–50 | 9

 2.1.5 Miscellaneous methods of preparing phosphines. Among re-
views relating to this section is an overview of the synthesis, properties
and catalytic applications of triethynylphosphines bearing bulky end-
capping groups, such as triarylsilyl and triarylmethyl, which provide a
deep metal-binding cavity117 and also a survey of the development of
core-functionalised chiral dendritic phosphines of interest as ligands
for asymmetric hydrogenation.118 The well-established Jugé-Stephan
ephedrine methodology for the synthesis of stereogenic phosphines
has been used in the synthesis of a series of P-stereogenic monophos-
phines having 2-p-terphenylyl and 1-pyrenyl substituents,119 and also of
various chiral phospha-indanes (58) and their 2- or 3-oxa analogues.120
Lithiation of imidazolinyl-bromoferrocenes followed by sequential treat-
ment with triphenylphosphite and TMSCF3/CsF are the key steps in the
synthesis of the air-stable chiral ferrocenylphosphines (59).121 A series
of new, air-stable chiral MOP-type tertiary phosphines (60), has been
obtained in one-pot procedures from the known air-stable primary
phosphine.122 The reactions of phosphine gas with diaryl-germylenes
or -stannylenes (Ar2M) result in both oxidative addition and arene elim-
ination reactions at the group 14 atom, with formation of germanium-
or tin- phosphorus-bonded compounds.123 Treatment of diphenylphos-
phine with sodium hydride, followed by addition of the sulfilimine
PhS(O)(NTs)CH2F, results in the formation of Ph2PCH2F in an efficent
and direct monofluoromethylation at phosphorus.124 Further application
of the reaction of secondary phosphines with 2,5-bis(dimethylamino-
methyl)pyrrole has given 2,5-bis(di-isopropylphosphinomethyl)pyrrole,
from which a variety of transition metal complexes has been pre-
pared.125 Further work has appeared on the isomerisation and chemis-
try of the phobane group of bicyclic monophosphines, with the
synthesis of a series of 9-butylphosphabicyclo[3,3,1]nonanes (61), of
which seven isomers have been identified in solution and several isol-
ated. NMR studies revealed unexpectedly high barriers to metal–
phosphorus bond rotation in complexes of this phobane group, behav-
iour that is similar to that of complexes of tBu2PR.126 Among other
monophosphines of interest prepared in various ways is a series of
mono-, di- and tri-boryl-phosphines (62), analogues of triarylphos-
phines, spectroscopic studies indicating that the diazaborinyl group
has donor properties similar to an alkyl group,127 2,3-disubstituted-2-
phospholenes (63) via catalytic cycloalumination of alkynes and subse-
quent phosphanation with dichlorophosphines,128 and a range of orga-
nophosphorus(III)-tellurium heterocycles.129 Among new diphosphines
and polyphosphines prepared is the diphospha-s-indacene-tetraone
(64),130 new carbocyclic and heterocyclic analogues of bis(di-t-butylphos-
phinomethyl)benzene, e.g., (65),131 and the branched tetrasilane-
substituted phosphines PhSi(SiPri2)3P and {PhSi(SiMe2)3}2P14.132 Also of
interest is a new route to the diphosphine monosulfides R2P–P(S)R2
(R ¼ Ph or Cy) by treatment of diorganochlorophosphines with lithium
sulfide in acetonitrile. On coordination to a ruthenium acceptor, the
diphosphine monosulfides rearrange to the bidentate ligands R2P–S–
PR2, sulfur mimics of 1,1-bis(diorganophosphino)methanes.133

10 | Organophosphorus Chem., 2016, 45, 1–50

 O
PX2

P N R R
Ph X Fe
P(CF3)2

(58) X = lp, BH3 or O (59) R = Ph, Pri, But or Bn (60) R = H or OMe;

X = Me, NH2, OMe
or PX2 = phosphiranyl
R
P R2
NH
B PPh3-n
P R2
NH
1
n R

(61) R = Bun, Bui, Busec or But (62) n= 1-3 (63) R1 = Me, Bu or Ph;
R2 = Et, Pr or Bu

O O
N
PR2
MesP PMes
PR2
N
PR12 NR22
O O

(64) (65) Ph or But (66) R1 = Cy or Ad;

R2 = Me or NR22 = piperidinyl

P(p-tolyl)2

PFc2
Ph2P OMe N N
Fe
NR2
N
N

(67)
(68) (69)

O But Ph Ph
S
PPh2 Ar NH
O N S R
O
B PPh2 PPh2
O

(70) (71) (72) linker N = imino or amido

Ph2P PPh2 O Ar Ar O
H2
Si
N N PR2
P P
N N O
B
O Ar Ar O O

(73) (74) (75) R = Ph, Cy or Ad

Organophosphorus Chem., 2016, 45, 1–50 | 11

 O O
BH3
PPh2
N
PBut2 N OEt NHPh
O N
X H H
Fe PPh2
S

(76) X = P(C6F5)2, NR2 or SR (77)

(78)
BH3 R
P N P
Et2P Ar PH2
Ar
N Ru
N N Ph R
N

(79) (80) Ar = 2-pyridyl or Fc (81)

R = alkyl or aryl

Applications of metal-catalysed routes for C–P bond formation in

phosphine synthesis have also continued to appear. The usual approach
is the reaction of aryl halides or triflates with a secondary phosphine
or chlorophosphine, catalysed by a palladium- or nickel-complex.
Palladium-catalysed procedures have been applied in the phosphanation
of aryl halides using primary or secondary phosphines in the synthesis of
the 3 0 -amino-2-diorganophosphinobiphenyls, (66),134 various ferrocenyl-
phosphines bearing amino- or alkoxy- groups, e.g., (67)135 and (68),136
and a series of arylphosphines bearing pyrazolyl-functional groups, e.g.,
(69).137 A palladium-catalysed phosphanation of a vinyl iodide was the
final step in the synthesis of the boron-functionalised phosphine (70).138
A nickel(II) complex-catalysed reaction of trimethylsilyl(diphenyl)pho-
sphine with aryl chlorides provides a very convenient route to a wide
range of arylphosphines.139 The mechanism of the copper(I)-catalysed
C–P coupling of diphenylphosphine with aryl halides has been the sub-
ject of a theoretical study, with particular reference to the identity of the
active catalyst, and the influence of solvent and ancilliary ligands.140
Also of interest is a study of the reactions of easily available carbyne
complexes of manganese with secondary or tertiary phosphines that
provide routes to back-bone-substituted diphosphinomethanes and re-
lated cyclic P-ylides.141
As in previous years, the elaboration of functional groups present in
substituents at phosphorus has led to a wide range of new phosphines.
Elaboration of phosphinobenzaldehydes and phosphinobenzoic acids
continues to be developed. New phosphines accessed in this way include
chiral sulfinamide monophosphines, e.g., (71)142 and chiral imino- and
amido- alkylsulfoxide ligands, e.g., (72).143 Similarly, the functional
group reactivity of phosphino-phenols and -thiols and phosphinoaryl-
amines and -alcohols has provided routes to a variety of C2-symmetric
bisphosphine ligands from tartaric acid,144 phosphine (thio)phenolate-
based half-zirconocene complexes (useful in ethylene-copolymerisation
reactions),145 and a,o-(phosphine–phosphite)polyether ligands.146 Sterically-
crowded triarylphosphines bearing anthra- and naphtho-quinone
substituents at carbon have been accessed by palladium-catalysed

12 | Organophosphorus Chem., 2016, 45, 1–50

Suzuki–Miaura coupling of arylboronic acids (derived from (bromoaryl)-
phosphines) with haloarylquinones.147 Among new arylphosphine-based
polymeric ligands accessed by aryl functional group modification
are a silica-gel supported system,148 various calcium carboxylate-based
coordination polymeric systems,149 and a silica nanoparticle-based
phosphine derived from 4-diphenylphosphinostyrene.150 Mono-lithiation
of triphenylphosphine ortho to phosphorus followed by treatment with a
series of silicon, germanium and tin alkoxides and halides has given a
series of compounds of the type {(o-Ph2P)C6H4}3MX (M ¼ Si, Ge, or Sn;
X ¼ F, Cl, H, or Me) involving a heptacoordinate group 14 atom, these
having received detailed structural study.151 Lithiation of 2-bromophe-
nyldiphenylphosphine, followed by treatment with tetraethoxysilane and
LiAlH4, has given the bis(phosphino)silane (73).152 The reactions of 1,2-
bis(phosphino)benzene with a bis(imine) and a bis(acyl halide) have
provided a series of easily accessible diphosphinobisdiazaphospholane
ligands, e.g., (74).153 Ortho-metallation of the aryl group of benzylphos-
phines with an iridium(I) complex provides a route to the ortho-
borylated phosphines (75).154 Side-chain reactivity of borane-protected
o-chloromethylbenzyldi(t-butyl)phosphine has provided routes to a range
of new o-xylylene-based ligands (76).155 Side chain development of
phosphinoferrocenyl aldehydes and carboxylic acids has also continued
to be used as a strategy for the synthesis of new phosphines. Among
new systems prepared in this way are various amido-functional
phosphines,156 including the squaramide (77),157 phosphino(alkenyl)-
ferrocenes,158 and 1 0 -(diphenylphosphino)-1-cyanoferrocene.159 New
diamidophosphite-functionalised arylphosphines have been obtained by
diamidophosphitylation of a range of phosphinophenols and phos-
phinoalcohols.160 Aminoalkylphosphines have also been used as key
intermediates in the synthesis of amido-functional phosphines. Recent
examples include N,N 0 -bis(2-diphenylphosphinoethyl)phthalimide,161
amide-linked phosphine-functional cyclodextrin-grafted polymers,162
and chiral thiourea-phosphines, e.g., (78).163 A versatile route has been
developed for the synthesis of 4-phosphino-1,2,3-triazoles, e.g., (79), from
the reactions of P-borane-protected C-silyl-protected alkynylphosphines
with azides.164 Also of note are two reports of the enantioselective re-
duction of acylphosphines to give chiral a-hydroxyalkylphosphines,
subsequently used in further derivatisation steps to give new chiral
phosphine ligands.165,166 Other work on the phosphitylation of hydro-
xyalkylphosphines has also appeared.167 Further studies have been
reported on the synthesis and chemistry of three-spoke dibridgehead
diphosphine stator complexes, formed initially by three-fold, catalytic
intramolecular ring-closing metatheses of the terminal alkenyl groups of
trans-[MCl2(P{(CH2)mCH¼CH2}3)2].168 Interest has also continued in the
in situ supramolecular generation of ion-paired chiral ligands from the
association of salts of phosphines bearing a quaternary ammonium
group with chiral phosphate anions.169
Mannich-type reactions involving ammonia or primary or secondary
amines with hydroxymethylphosphonium salts, hydroxymethyl-
phosphines or primary and secondary phosphines (in the presence of

Organophosphorus Chem., 2016, 45, 1–50 | 13

formaldehyde) have continued to be used to generate new amino-
methylphosphines. New aminoalkylphosphines reported include com-
pounds of the type (Ph2PCH2)2NAr (Ar ¼ o-F3CC6H4 and m-F3CC6H4)170
and (Cy2PCH2)3N,171 diphenylphosphinomethylamino-functionalised
derivatives of ciprofloxacin and norfloxacin antibiotics,172 various
8-membered ring systems of type (80)173,174 and a series of macrocyclic
tetrakisphosphines involving 14 to 20-membered rings by the stereo-
selective self-assembly of ao-bisphosphines, formaldehyde and benzyla-
mine.175 The range of stabilised primary and secondary phosphines
bearing ferrocenyl or ruthenocenyl substituents has been extended.
Alkylation of FcCH2P(CH2OH)2 with MeI or p-nitrobenzylbromide, or of
CyP(CH2OH)2 with FcCH2NMe31I, gave new hydroxymethylphosphines,
which, on treatment with Na2S2O5, gave new secondary phosphines of the
type FcCH2PHR (R ¼ Me, Cy or p-O2NC6H4). Similar reactions of bro-
moalkylferrocenes Fc(CH2)nBr (n ¼ 4, 6 or 11) led to the isolation of
Fc(CH2)6PH2. This study also reported the synthesis of the first ru-
thenium-derived primary phosphine (81).176

2.2 Reactions
2.2.1 Nucleophilic attack at carbon. The formation of zwitterionic
phosphonium compounds by nucleophilic attack of phosphorus at un-
saturated carbon and the subsequent engagement of such dipolar spe-
cies in C–C and C–N bond-forming reactions continues to attract a
great deal of attention. A recent general review of the application of
chiral phosphines in nucleophilic organocatalysis has appeared.177 Also
reviewed is the use of phosphine catalysts to promote transformations
of alkynals, alkynones, propiolates and related electron-deficient al-
kynes.178 Further examples have appeared of the reactions of tertiary
phosphines and acetylenedicarboxylic acid esters in the presence of a
third reactant, commonly a proton source that serves to protonate the
initial dipolar species formed to give vinylphosphonium cations. These
may then undergo addition of an anion derived from a proton source
(or addition of another nucleophilic species) to form a new phospho-
nium ylide. In many cases, these are stable, but some undergo intramo-
lecular reactions to give new, non-phosphorus-containing products,
often via a Wittig route. Further examples have also appeared of reac-
tions of this type that lead to C–C bond formation with eventual refor-
mation of the phosphine, the latter now assuming a catalytic role. The
formation of stable ylides from the reactions of triarylphosphines, di-
alkyl acetylenedicarboxylates (DAAD) and various reagents has been
investigated using aroyl isocyanates,179 N-acetylarylidenehydrazides,180
N-ethyl-N 0 -propionylurea or N-acetylthiourea,181 and 3-(aroylmethylene)-
1,3-dihydro-2H-indol-2-ones.182 Reactions of these types involving a
catalytic role by the phosphine, or alternatively a Wittig-like elimination
of the phosphine oxide, have led to syntheses of highly-functionalised
2,5-dihydropyrroles,183 4-oxo-2,5-cyclopentadienes,184 and ring-expansion
products from sulfamate-derived cyclic imines.185 Further kinetic
studies have also been reported for the formation of stable ylides in

14 | Organophosphorus Chem., 2016, 45, 1–50

reactions of this type, this time involving a pyridazinone as the proton
source, again showing that the rate-determining step is nucleophilic
attack by the phosphine at the alkyne carbon, followed by a fast proton
transfer.186 Also reported is a multi-pronged mechanistic study of the
phosphine-mediated conjugate addition of an alcohol to an acetylenic
ester, using a pressurised sample infusion electrospray ionization
mass spectrometry technique, together with 31P- and 1H-NMR spectro-
scopy.187 The reactions of tertiary phosphines with a much wider range
of molecules bearing an alkyne functional group have also been stud-
ied, mainly from the standpoint of the role of the phosphine as a cata-
lyst in promoting cycloaddition (and other) reactions. Included among
these are nucleophilic conjugate addition of phosphines to oligoyno-
ates, and subsequent reactions with aldehydes to form new ylides,188
routes to spiro[cyclopentane-1,3 0 -indolines] and spiro[cyclopent[2]ene-
1,3 0 -indolines],189 multicomponent reactions of phosphines, diynedioates
and aryl aldehydes providing trisubstituted furan-based phosphonium
ylides,190 a regio- and stereo-selective hydrocarboxylation of enynes,191
annulation reactions of 2-butynoates and a-ketoesters leading to
cyclopentene derivatives,192 and routes to 4-arylidene-5-imidazolones,193
quinolones,194 spirocyclopentanones,195 Z-enediynes,196 and fluorescent
g-lactams.197 Also reported is a phosphine-catalysed anti-carboboration
of alkynoates with alkyl-, alkenyl- and aryl-boranes.198 Arynes have also
figured in phosphine-catalysed three-component reactions with carbonyl
compounds which lead to new stable pentacovalent phosphoranes based
on the benzoxaphosphole system.199
Very many other phosphine-catalysed reactions, in which the initial
step is the formation of a reactive phosphoniobetaine intermediate by
addition to carbon–carbon multiple bonds, in particular alkenes, dienes
and a-substituted allenoates, the zwitterion then being trapped by a
suitable electrophile, have been reported in the year under review. Also
included in this category are reactions leading to carbon–carbon bond
formation as typified by the Morita–Bayliss–Hillman (MBH) and related
aza-MBH reactions. Nucleophilic phosphine catalysis of the reactions of
allenes with electrophiles has been the subject of a review.200 Allenoates
and enones form cyclopentenes via a phosphine-catalysed [3 þ 2]
cycloaddition whereas the corresponding amine-promoted reaction
proceeds via a [2 þ 4] cycloaddition to give dihdropyrans or pyrans.
A computational study of these reactions has attributed the difference in
part to the greater stability of the phosphorus-ylide adduct compared to
the corresponding ammonium-ylide.201 A related study from the same
group has investigated the activation of allenoates by a wide range of
Lewis bases in terms of stereochemical aspects and solvent effects.202
The addition of phosphines to 5-hydroxy-2,3-dienoates also follows a
different course to that with DABCO, enabling a Lewis base divergent
isomerisation and dictating the course of subsequent reactions.203
The use of chiral phosphines as catalysts providing control of the
stereochemical outcome of cycloaddition reactions of allenoates
continues to develop. Recent examples include the use of aminoacid-
functionalised alkyldiphenylphosphines in an asymmetric synthesis of

Organophosphorus Chem., 2016, 45, 1–50 | 15

spiropyrazolones204 and an enantioselective g-addition of 3-substituted
oxindoles,205 chiral biphenyl-derived phosphepines (82) in enantio-
selective [4 þ 1] annulations to form functionalised cyclopentenes,206
and the spiro-monoarylphosphine (83) in an enantioselective [4 þ 2]
cycloaddition of ketimines which provides access to a tetrahydropyridine
framework with a chiral tetrasubstituted stereogenic carbon centre, with
excellent regioselectivity.207 The efficiency of a wide range of chiral
phosphines has been investigated in the catalysis of asymmetric [3 þ 2]
cycloadditions of C,N-cyclic azomethine imines with d-substituted
allenoates, affording tetrahydroquinoline frameworks with good dia-
stereo- and enantio-selectivities under mild conditions. The most effec-
tive catalyst was the chiral bisphosphinoferrocene (84).208 Among
cycloaddition reactions of allenoates catalysed by simple achiral mono-
phosphines, usually tributyl- or triphenyl-phosphine, are additions of
cyclic 1,2-diones for benzannulations leading to polycyclic aromatic
hydrocarbons,209 and other annulation reactions leading to bicyclic cyclo-
penta[b]dihydrofurans,210 aza-bicyclo[3,3,0]octanes,211 bicyclo[3,3,0]-
212
octenes, polysubstituted 2,5-dihydrofurans and cyclopentenes,213 and
sulfamate-fused tetrahydropyridines.214 Phosphine-catalysed cycloaddition
reactions of 1,2-allenic ketones,215 and a self-catalysed reaction between the
diphosphinoketimine (Ph2P)2C¼C¼NBut and electron-poor alkenes,
leading to highly functionalised l5-phospholes,216 have also been
reported. Phosphine-catalysed cycloadditions of many other types of
unsaturated substrate have been reported in the year under review.
Again, asymmetric cycloadditions have been facilitated by the use of
chiral phosphines and the general area has been reviewed.217 Recent
applications include routes to spirocyclic systems, catalysed by
aminoacid-functionalised alkyldiphenylphosphines218 and ether-
functionalised triarylphosphines,219 b-lactones from ketenes and
aldehydes, catalysed by the BINAPHANE bis(dinaphthophosphepin) lig-
and,220 and the asymmetric [3 þ 2] cycloaddition of MBH carbonates with
maleimides, catalysed by chiral aminoalkylferrocenylphosphines.221 The
rate of the intramolecular MBH reaction has been shown to be enhanced
by the use of a combined catalyst consisting of a tertiary phosphine (or
amine) nucleophile and 1,3-diphenylthiourea.222 A phosphine-catalysed
aza-MBH reaction between acrylates and ketimines derived from isatins
has been developed using the squaramide-functional phosphines (85).223
Phosphine-catalysed annulation reactions involving MBH carbonates
and phosphates have also been developed, leading to bicyclo[4,1,0]-
heptenes,224 chromenones,225 isoxazoline N-oxides,226 2-methyl-2H-
pyrans and 2-oxabicyclo[2,2,2]oct-5-enes,227 trifluoromethylated
228
g-butenolides, spirocyclopenteneoxindoles229 and spirooxindoles.230
Among a miscellany of other applications of tertiary phosphines in
nucleophilic catalysis are routes to carboxylated 1H-indoles and
2H-pyran-2-ones,231 functionalised pyrrolidines,232 dinitrogen-fused het-
erocycles,233 azaspiro[4,4]nonenes,234 trifluoromethyl-substituted pyr-
roles,235 functionalised b-acetamidocarbonyl compounds,236 conversion
of cyclopropenones to allenes,237 and procedures for annulations of

16 | Organophosphorus Chem., 2016, 45, 1–50

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