doi.org/10.1002/ajoc.

202100650 Review
www.asianjoc.org

Benzils: A Review on their Synthesis

Saba Kauser J. Shaikh, Ravindra R. Kamble,* Praveen K. Bayannavar, and
Mahadevappa Y. Kariduraganavar[a]

Asian J. Org. Chem. 2022, 11, e202100650 (1 of 46) © 2021 Wiley-VCH GmbH

Abstract: This review segregates and outlines all the aspects
of the synthesis of Benzil for almost two centuries. Here, state
of the art review includes the early synthesis in 1836 to the
advancement made over the past years in the knowledge of
the preparation of benzil derivatives till the present. Benzil is
one of the important and highly underrated organic com-
pounds in which two adjacent carbonyl groups are flanked
by two phenyl rings. Apart from its diverse functionality, the
1. Introduction
Benzil 1 (Figure 1) is one of the eloquent organic compounds
consisting of two adjacent carbonyl groups flanked by two
phenyl rings. The IUPAC nomenclature consistently designates
benzil as 1,2-diphenyl-1,2-dione with the molecular formula
C14H10O2. Also known as bis-benzoyl, or diphenylglyoxal, benzil
belongs to a class of compounds known as stilbenes. These are
the organic compounds containing 1,2-diphenyl ethylene
moiety containing dicarbonyl system with the general formula
RCO COR (R=C6H5). Regarded as one of the most common
diketones, benzil appears as a yellow crystalline solid with a
melting point 94–95 °C and high boiling point 346–348 °C/
12 mm. With pKa 8.6, benzil is an extremely weak basic
(essentially neutral) compound. Benzil has a dipole moment of
3.89 Debye and the ionization potential of 7.7 and 7.5 eV
(vertical and adiabatic, respectively) (polarisable continuum
model, PCM).[1] Benzil dissolves in ethanol, ether, benzene, but
does not dissolve in water.
Significance of benzil, however, is not limited to classic
Benzil-Benzilic rearrangement in the connection of the synthesis
of A-Norpregnanes, classified as A-Norsteriods.[2] Benzil and its
derivatives are widely used in the dyes, sensitizers in organic
photovoltaics, biomarkers, fluorescence probes, as well as
synthons in the synthesis of heterocycles having biological and
therapeutic applications.[3] In particular, it is frequently used in
the free-radical curing of polymer networks, viz., decomposed
by ultraviolet radiation that facilitates free-radical species within
the material, leading to the formation of cross-links. Benzil is
normally utilized as a photoinitiator in polymer chemistry.[4]
Benzil has also demonstrated selective inhibition of human
carboxylesterases, which are involved in the hydrolysis of
carboxylesters and many clinically used drugs.[5]
Figure 1. Benzil structure.
[a] Dr. S. K. J. Shaikh, Prof. R. R. Kamble, Dr. P. K. Bayannavar,
Prof. M. Y. Kariduraganavar
Department of Studies in Chemistry, Karnatak University, 580003 Dharwad
(India)
E-mail: kamchem9@gmail.com
ravichem@kud.ac.in
Asian J. Org. Chem. 2022, 11, e202100650 (2 of 46)
Review
reactivity of benzils proclaims its prospects as a reagent for
the synthesis of various heterocycles. On recasting benzil, it is
possible to obtain a wide variety of utilities in pharmaceut-
icals, polymer, and material chemistry. This contemplation of
the review gives a general perspective of reaction routes,
mechanisms and highlights the conversions due to oxidation,
and accentuates benzil as an emerging putative target.
The vast scope of synthesized benzil is well referenced and
published in a wide range of scientific journals and scientific
data concerning the potential relevance of benzil derivatives in
the literature were analyzed.
2. Structure of Benzil
The two carbonyl carbon atoms have bond length of 1.54 Å,
indicating the absence of π-bonding between these two
carbonyl centres. The structural conformation of benzil 1 has
interested chemists for many years. Glyoxal, the simplest
molecule of this type, R=H, has been reported to exist as two
different forms with the carbonyl groups anti 2 or syn 3 to each
other.[6–8] When the two hydrogen atoms are replaced by alkyl
groups, as in 2,3-butanedione (biacetyl), the anti form 4 is the
only stable conformer (Figure 2).
Non-planar forms have also been observed eg., in oxalyl
chloride (R=Cl) and oxalyl bromide (R=Br).[9–10] Oxalylchloride
exist in the vapour phase as a mixture of anti 5 and gauche 6
conformers shown in Figure 3. The non-planar form has been
rationalized in terms of repulsive forces (such as non-bonded
repulsion, electron-pair repulsion, and dipole-dipole repulsion)
being larger than the conjugation stabilization in the syn
configuration. But in all of these molecules the most stable
form has been found to be the planar anti 5.[11]
In benzil (R=C6H5) the phenyl rings introduce two important
factors into the α-dicarbonyl system: (a) they are bulky and
hence sterically important, and (b) the K-orbitals in the phenyl
ring can interact with the carbonyl K system and hence
influence the conjugation in the O=C C=O system. This affects
the conformation of benzil and makes it different from other
RCO COR systems. The two bulky phenyl rings cause the steric
interaction and also the interaction between the carbonyl
groups and the π-orbitals modify the conjugation. One form
characterized by torsion angle (θ = 110°) has been observed
and the θ = 0° and θ = 180° correspond to planar cisoid 7 and
Figure 2. Structure of dicarbonyl compounds.
© 2021 Wiley-VCH GmbH

transoid 8 conformations. The benzil molecules doped in
biphenyl crystal possess both the skewed and planar trans
configurations 8.[12] When the two carbonyl groups are in the
trans orientation the calculated dipole moment is negligibly
small (μ = 0.07 D) indicating a near planar geometry having a
centre of symmetry.
The cis conformer has a large dipole moment of 5.26 D. The
minimum skewed configuration of benzil has a dipole moment
of 3.89 D.[13] The electron diffraction experiments indicate that
the O=C C=O torsion angle θ = 117° which was further
supported by MM3 force field studies with θ = 109°. However,
spectral data indicated the existence of both cisoid 7 and
transoid 8 forms in solution (Figure 4). For example, the splitting
of carbonyl band in the IR spectrum was due to two rotational
isomers. The band with highest frequency was due to cisoid
form and due to C2 symmetry in benzil exhibited a doublet in
Ravindra Kamble received his BSc
(1995) and MSc (1997) in First Class
with Distinction from Karnatak Univer-
sity Dharwad and completed his PhD in
the year 2001. He joined the Depart-
ment of Chemistry, Yuvaraja’s College,
University of Mysore, Mysuru as Assis-
tant Professor and then he moved to
Karnatak University, Dharwad as Asso-
ciate Professor in 2008 and was ap-
pointed as Full Professor in the year
2014. He visited Institute of Chemistry,
University of Debrecene, Debrecene,
Hungary under Indo-Hungarian Educa-
tional Exchange Program in the year
2012 and was Sir C. V. Raman Post-
Doctoral Fellow at SD State University,
Brookings, USA during the year 2016–
2017. His research interests include
synthetic chemistry, medicinal chemistry
and design of dyes for solar cells.
Saba Kauser J. Shaikh received her
Bachelor’s degree in 2011 and Master’s
degree in Chemistry in 2013 both in
First class with Distinction from Karna-
tak University, Dharwad, India. Later
she joined Prof. Ravindra R. Kamble’s
research group in 2014 and mainly
worked on the development of synthetic
methods in N-alkylation, one-pot multi-
component reactions, including greener
methods & microwave methods. In the
year 2019, she obtained her Doctor of
Philosophy from Karnatak University,
Dharwad. She is currently working as
tenure track Professor at the Depart-
ment of Chemistry, Karnatak University,
Dharwad. Her research interests include
the synthetic chemistry of nitrogen and
sulphur heterocycles and their antifun-
gal and anticancer activities.
Asian J. Org. Chem. 2022, 11, e202100650 (3 of 46)
Review
the carbonyl region in the IR spectrum.[14] The conformation of
benzyl depends upon the dipole moment of solvents (μ). With
increase in the polarity of the solvent, cisoid conformation of
benzil was favoured.[15]
3. Methods of Synthesis of Benzils
Benzils were found in numerous bioactive scaffolds. Benzil
derivatives are important key intermediates in a wide range of
organic syntheses, especially for the construction of various
heterocyclic compounds and in the compounds having material
applications. Several synthetic strategies have been reported to
obtain this useful structure and will be dealt in the following
sections discussed below.
Praveen K. Bayannavar has completed
his Bachelor’s degree from Karnatak
University, Dharwad and Master’s de-
gree in Chemistry from Rani Channam-
ma University, Belagavi in the year
2014. In the year 2016, he joined Prof.
Ravindra R. Kamble’s research group
and mainly worked on the synthesis of
novel heterocycles of pharmacological
importance and organic molecules for
photovoltaic applications. He received
his Doctor of Philosophy degree in the
year 2021, from the same university. He
is currently working as tenure track
Professor at Department of Chemistry,
Karnatak University, Dharwad. His re-
search interests include synthesis of
novel heterocycles, development of syn-
thetic methods, solar cell applications
and pharmacological applications.
Mahadevappa Y. Kariduraganavar ob-
tained his Doctor of Philosophy in
Chemistry in 1993 from Karnatak Uni-
versity, Dharwad, India. Currently, he is
working as Professor & Chairman in the
same University. He is an awardee of a
prestigious Common Wealth Fellow and
under this fellowship program he did
Post-Doctoral Research at J. J. Thomson
Physical Laboratory, Department of
Physics, University of Reading, UK in
2007–2008. He has also developed 14
prototype devices on Fuel Cell, Super-
capacitor and Electrodialysis and ob-
tained 2 US Patents on Ion-Exchange
Membranes. His research interests in-
cludes: Pervaporation Membranes, Ion-
Exchange Membranes, Nonlinear Opti-
cal (NLO) Materials, Dendrimers, Shape-
Memory Polymers, Direct Digital Manu-
facturing (DDM) in Tissue Engineering,
Tumour Targeted Blood-Brain Barrier,
Fuel Cell, and Supercapacitor.
© 2021 Wiley-VCH GmbH
 Review

Figure 3. Anti and gauche conformers of oxalylchloride.

3.1. Oxidation of α-hydroxyketones (Benzoins)

A systematic review containing summary of the literature data

Figure 4. Rotational isomers of Benzil.
Scheme 1. Oxidation of benzoin 9 to benzil 1.
on the oxidative methods for the synthesis of di-carbonyl
compounds with preservation of the carbon skeleton of the
starting substrates is reported by Filiminov et al.[16] Benzil is
generally synthesized by the oxidation of benzoin 9
(Scheme 1)[17] using the reagents such as chlorine,[18a] nitric
acid,[18b] electrolytically,[18c] catalytically[18d] and iodine,[18e] and
also from desoxybenzoin using SeO2[19a–b] and aqueous HBr in
DMSO.[19c] The oxidation of benzoins is one of the most efficient
and practical methods for the synthesis of benzils. Under
relevant reaction conditions, commonly used oxidants are listed
in Table 1.
Other reagents which are mild in nature are also used for
the oxidation of benzoin to benzil 1. Such examples include
oxidation of benzoin using benzeneseleninic anhydride in

Table 1. Oxidants and reaction conditions reported for the conversion of benzoin to benzil 1.
Reagent Temperature [°C] Solvent Time [h] Yield [%] Ref.

Thallium nitrate reflux glyme/H2O 2 95 [20a]

Copper sulphate 95 H2O 2 86 [20b]
Copper acetate reflux HNO3 1 90 [20c]
Ammonium nitrate-copper acetate reflux CH3COOH/H2O 1.5 90 [20d]
Bismuth nitrate-copper acetate reflux CH3COOH/H2O 3 99 [20e]
Silica supported-ferric nitrate reflux C2H4Cl2 3 93 [20f]
Ferrous-cysteine peptide complexes stir/25 DMF 20 55 [20g]
Ferrous thiolate 25 DMF 25 93 [20h]
Ferric oxide-aluminium oxide 80 Pyridine 1 98 [20i]
VOCl3 r.t. Acetonitrile 1.5 94 [20j]
Chromium trioxide on Kieselguhr r.t. DCM 1 98 [20k]
Chromium trioxide under viscous conditions r.t. DCM 2 86–96 [20l]
Silica-supported manganese dioxide reflux DCE 10-14 86–94 [20m]
Ammonium chlorochromate on alumina 58 Cyclohexane 14 92 [20n]
Ammonium chlorochromate on silica 60 Cyclohexane 14 95 [20o]
Alumina or silica gel 140/MWI Homogenised on mortar 3/5 min 100 [20p]
Alumina-supported active MnO2 r.t. DCM 2 80 [20q]
Commercial alumina r.t. DCM 2.5 67 [20r]
Nano-MgO 100 Acetonitrile 1 80 [20s]

Asian J. Org. Chem. 2022, 11, e202100650 (4 of 46) © 2021 Wiley-VCH GmbH

presence of THF, resulted benzil at 92% yield in 3 hours.[21] On
the other hand, a prompt attempt for an oxygen-transfer
reaction was achieved by a less acidic and stable reagent
quinolinium fluorochromate (QFC) which readily oxidizes
benzoin to benzils.[22] Trichloromelamine (TCM) selectively
oxidizes benzoin to benzil in CH2Cl2 with higher yields, but with
the longer duration due to the steric effects.[23] Also, when
benzoin was oxidised at moderate temperatures by bismuth
oxide specifically with acetic acid in 2-ethoxyethanol, gave an
excellent yields of benzil.[24] The permanganate reagents are
used for the oxidation of various alcohols and acyloins to the
corresponding carbonyl compounds. Amongst all barium
permanganate is reported as a mild and effective oxidising
agent. Ba(MnO4)2 in presence of acetonitrile yielded efficient
amount of benzil in less duration.[25] Firouzabadi et al.[26]
reported the multi-utility of barium ferrate monohydrate for
oxidizing various organic compounds and has remarkably
converted benzoin to benzils with good yields.
Also, NaBrO3 & AgBrO3 which are cheap, commercially
available or can be easily prepared are used for the oxidation of
series of the organic substrates in presence of Lewis acid to
give benzil at affordable yields.[27] Oxidation reactions are
developed for the purpose of obtaining oxidizing agents in
mild, neutral and aprotic solvents, so Cr(VI) based oxidants are
reported. Chromium bipyridyl peroxide could easily oxidise
benzoin in 90% yields to benzil as reported by Firouzabadi
et al.[28] Periodic acids are known as strong oxidizing agents,
and tetrabutylammonium periodate (TBAPI)[29] is able to oxidize
benzoin to benzils in presence of Lewis acid and aprotic organic
solvents. The ultra-centennial o-Iodoxybenzoic Acid (IBX) was
reported as a valuable oxidant for the better conversion of
benzoin into benzil.[30] Certain other reagents such as Fe(NO3)3
impregnated on acidic montmorillonite,[31] K2FeO4,[32] titanium
isopropoxide,[33] benzyl triethylammonium tribromide,[34] triphe-
nylantimony dibromide (Ph3SbBr2),[35] Ph3PBr2[36] and PhMe3N +
Br3 . NBS[37] are used to oxidize benzoin to benzil 1 in a
quantitative yield.
Scheme 2. Simultaneous metal-salen formation and oxidation of benzoin 9 to benzil 1.
Scheme 3. Preparation of Schiff base complex of Mn(II) 10 followed by oxidation of benzoin 11 using H2O2 catalyzed by 10 to form benzil 12.
Asian J. Org. Chem. 2022, 11, e202100650 (5 of 46)
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The metal-salen complexes (metal = Mn, Cr, Fe, Ru, Co, V
and Ti) find widespread applications as efficient catalysts for the
selective oxygenation of alkenes, organic sulfides, sulfoxides
and aromatic amines. In view of this, metal-salen catalyzed
oxidation of benzoin to benzil has been reported by Kangyuan
et al.[38] This is an example of green protocol for the simulta-
neous formation of [Metal (Salen)] viz., Co, Cu, Zn, Fe and Mn
which efficiently oxidizes benzoin 9 present in the reaction
mixture to benzil 1 in one-pot. It was observed that these
metal-salens [Co (Salen)] gave a yield of 76.5% and can be used
for 5 times (Scheme 2).
A similar kind of simple, highly efficient and mild catalytic
oxidation of benzoins to the corresponding benzils was
developed using manganese (II) schiff base complex 10 as novel
and reusable catalyst in acetonitrile as solvent and H2O2 as
green oxidant has been reported.[39]
Scheme 3 illustrates the formation of Schiff base complex of
Mn(II) 10. Using this complex a simple and convenient method
for the oxidation of benzoin derivatives 11 to the correspond-
ing benzils 12 was achieved under mild conditions in H2O2 at
room temperature. H2O2 is an inexpensive and environmental
friendly oxidant. It is observed that the homogeneous catalyst is
very active in high conversion rate of benzoin 11 to benzil 12.
The easy removal of the catalyst makes this reaction better
compared to other homogeneous catalyst. Moreover, the
catalytic oxidation can be carried out at room temperature in
short reaction time with high yield and purity. Optimization of
the reaction indicated that the substrate to oxidant ratio of 1 : 2
and 0.01 m mol of the Mn(Salen), the best yield of benzil (98%)
was observed. From the results in Table 2, it seems that the
benzoins 11 containing electron-donating group were found to
be more reactive and could be oxidized more easily (b and f). In
contrast, the benzoins 11 containing electron-withdrawing
group have shown lower reactivity (j). This shows that the
electronic effects of substituents have a significant role in the
oxidation.
However, one-pot benzoin condensation followed by air
oxidation has been reported under atmospheric oxygen. The
© 2021 Wiley-VCH GmbH

Table 2. Effect of substituents on the yields of oxidation of benzoin to
benzil by H2O2 using Mn(Salen) as a catalyst.
Entry No. Ar1 Ar2
a phenyl phenyl
b p-anisyl p-anisyl
c p-aminomethyl phenyl
d p-tolyl p-tolyl
e p-anisyl phenyl
f 2-pyridyl 2-pyridyl
g 2,4-dimethoxyphenyl 2,4-dimethoxyphenyl
h phenyl m-anisyl
i phenyl p-tolyl
j p-tolyl m-bromophenyl
reaction was preceded by the catalytic effect of cyanide ion in
respective alcoholic solvents under atmospheric O2. By this
method, various aromatic aldehydes 13 such as 4-anisaldehyde,
4-bromobenzaldehyde, 3-nitrobenzaldehyde and 2-furylcarbal-
dehyde were directly transformed to the respective benzil
derivatives 14 in moderately good yields. However, this
procedure was unsuccessful in case of 4-methylbenzaldehyde,
4-chlorobenzaldehyde, 4-pyridinecarbaldehyde and 2-pyridine
carbaldehyde as shown in Scheme 4.[40]
3.2. Oxidation of diarylalkynes (Tolanes)
Due to the growing application of benzils in the synthesis of
nitrogen heterocycles and material applications, their synthesis
has been extensively explored in the last three decades by the
synthetic organic chemists. Importantly, an easy access to
diarylalkynes (tolanes) 15 was by Sonogashira-Linstrumelle
couplings and other C C bond forming reactions to obtain the
alkynes followed by the oxidation of diarylalkynes. This has
become an expedient method for the formation of benzil
derivatives 1 and this protocol has been reported intensely
(Scheme 5). Oxidation of alkanes, alkenes and alkynes etc. has
been systematically reviewed by Fatiadi.[41] The method of
oxidation of diarylalkynes to benzil derivates developed due to
this a plethora of oxidizing reagents came into light has been
summarized under Table 3. In this regard, an extensive review
focused mainly on the oxidation of alkynes under various
catalytic conditions leading to the synthesis of benzils viz.,
di(het)aryl-1,2-diketones is reported by Yuan et al.[42]
Scheme 4. Oxidation under atmospheric oxygen by one-pot method.
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Yield [%]
98
91
70
78 Scheme 5. Oxidation of diarylalkynes 15 to benzil 1.
85
89
73
58
84
45
Scheme 6. Oxidation of diarylalkenes 16 to benzil 1.
3.3. Oxidation of diarylalkenes
As discussed above, diarylalkynes have been subjected to
oxidation under various catalytic systems and have been
observed to form the benzil derivatives efficiently. Hence, the
oxidation of substituted alkynes form a typical method for the
preparation of benzil derivatives and for this various catalytic
systems have been built in previous years, mainly containing
transition metals in combination with oxidants. Interestingly,
alkenes are cheaper and more easily available than alkynes.
Therefore, the oxidation of stilbenes 16 provides a simple and
efficient route to benzil derivatives 1 (Scheme 6) in both
academia and industry. Initially, stoichiometric amounts of
oxidizing reagents such as KMnO4 and SeO2 with some acids
were frequently used which easily led to the cleavage of the
C C bond. Also, the epoxidation, dihydroxylation, aminohydrox-
ylation, and the Wacker reaction have all been widely applied in
organic synthesis.
However, Sharpless and co-workers[98] reported the
permanganate/acetic anhydride mediated oxidation of open
chain and cyclic alkenes to get the 1,2-diketones. The trans and
cis-stilbenes were subjected to the oxidation to get the benzils
in 46 and 60% yield, respectively. Along with this keto acetate
was observed to be a minor product. Sometimes there is a
possibility of complete cleavage of C=C. Further, Yusubov
et al.[99] designed a protocol for the conversion of diarylalkenes
17 to benzils 18 for which they used HBr and DMSO as shown
in the Scheme 7 below. Initially, the authors compared this
reaction by treating the alkynes with HBr and DMSO in
© 2021 Wiley-VCH GmbH
 Review

Table 3. Oxidants classified for the conversion of diarylalkynes 15 to benzil 1.

Sec. No. Catalyst/Reaction Conditions Yield [%] Ref.

3.2.1. Transition-metal catalyzed oxidation

3.2.1.1. Mercury-catalyzed oxidation Hg(NO3)2. H2O, DMF/air, 22 °C 90 [43]
3.2.1.2. Rhenium-catalyzed oxidation Me3ReO3/H2O2, Alcohol, r.t. 69–80 [44]
3.2.1.3. Ruthenium-catalyzed oxidation i) [Ru(cymene)Cl2]2, I2, TBHP, Dioxane, 80 °C, 12 h 93 [45]
ii) [Ru(cymene)Cl2]2, TEMPO, Oxone, MeNO2/H2O 80–94 [46]
iii) RuCl3, NaIO4, NaHCO3, MgSO4, MeCN/H2O, r.t. 62–95 [47a]
iv) RuCl3,NaOCl, Et2CO3 64–83 [47b]
3.2.1.4. Copper-catalyzed oxidation i) Cu(0)/Selectfluor, MeCN/H2O, air, r.t. 64–93 [48–49]
ii) CuI/Cu(OTf)2, Cs2CO3, DMSO, 140 °C, 6 h; aq. HI, 140 °C, 6 h 54–89 [50–51]
iii) CuI, Na2S2O8, DMSO, 140 °C, 24 h, air 65–89 [52]
iv) Cu(OTf)2, PhI(OAc)2, HOAc/HFIP 90 [53–54]
3.2.1.5. Gold-catalyzed oxidation i) AuCl/AgSbF6, DCE, reflux 74-98 [55]
ii) Ph3PauNTf2, Selectfluor, MeCN/H2O, 80 °C, 24 h 80 [56]
3.2.1.6. Chromium-catalyzed oxidation ZnCr2O7.3H2O/CCl4, r.t. 50 [57]
3.2.1.7. Iron-catalyzed oxidation i) FeBr3, DMSO, 200 °C, MWI 80 [58]
ii) FeCl3, DMAP, MeCN/H2O, 4 h, r.t. > 99 [59]
3.2.1.8. Palladium-catalyzed oxidation i) PdCl2, DMSO 80–98 [60–62]
ii) PdCl2, CuCl2, DMSO, O2, 100 °C, 5–16 h 81 [63]
iii) Pd/C, O2, DMSO, 120 °C, 24 h 92 [64]
iv) PdI2, DMSO, 140 °C 57–98 [65–66]
v) PdCl2, pyridine-N-oxide, 120 °C, 24 h, air 95 [67]
3.2.2. Inorganic reagents based oxidation
3.2.2.1. Potassium Permanganate i) KMnO4/H2O, CO2, 25 °C 92–96 [68]
ii) KMnO4, Adogen 464 (PTC in acetic acid) 93 [69]
iii) Powdered KMnO4,[70] MgSO4, NaHCO3, aq. acetone, r.t. 88 [71]
3.2.2.2. I2, I +, and NIS i) I2, DMSO, 155 °C, 1–6 h 90–93 [72–79]
ii) I2, H2O, MeCN, r.t. 63–93 [80]
iii) NIS/ H2O, MeCN, 70 °C 62 [81]
iv) NH4I/EtOCS2K, DMSO, H2O, 130 °C 63–95 [82]
v) PhI(OCOCF3)2/I2 (PIFA), THF/H2O, 40 °C 45–56 [83]
3.2.2.3. Sulfur Trioxide SO3, Dioxane, H2O, 66 °C 19–99 [84]
3.2.2.4. Methanesulfonic acid HCOOH, CH3SO3H, DMSO, HBr, H2O 56–84 [85]
3.2.2.5. Cerium Ammonium Nitrate (CAN) i) CAN, Argon, MeCN 23 [86]
ii) CAN, MeCN CH2Cl2 78–95 [87]
3.2.2.6. Thallium nitrate (TTN) TTN, Acidic glyme or CH3COOH 45–97 [88]
3.2.2.7. Potassium Peroxymonosulfate (Oxone) Oxone[90]/TFA, 0 °C to r.t., 15–30 min 15–90 [89]
3.2.2.8. Ozone Ozone, DCM/Acetone, PPh3, 78 °C 80–95 [91]
3.2.3. Wacker-Type oxidation[92]
i) PdBr2, CuBr2, 1 atm O2, Dioxane/H2O, 60 °C, 24 h 67–97 [93]
ii) Pd-Fe3O4, CuBr2, O2, 95 °C, 77–98 [94]
1,4-Dioxane:H2O, 24 h
3.2.4. Photo-oxidation[95]
i) Eosin Y, 4-chlorobenzenethiol, MeCN, air, r.t., 8 h, hν (blue LED) 55–86 [96]
ii) O2, hν (visible), MgBr2. OEt2, MeCN, r.t. 30–71 [97]

Scheme 7. High-yield oxidation of corresponding stilbenes with the system HBr-DMSO.

Table 4. Oxidation of stilbenes using HBr-H2O2-DMSO system.

presence of another oxidant H2O2 as presented in Tables 4 and
5 below. Entry No. Ar1 Yield [%]
Oxidation of stilbenes 17 with HBr-DMSO proceeded with 18 a phenyl 70
high selectivity. The temperature below 110 °C slowed down 18 c p-chlorophenyl 76
18 f p-nitrophenyl 66
the reaction and electron donating groups and Br at para
position of phenyl ring enhanced the reaction where as the
electron withdrawing groups declined the rate of reaction as

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 Review

Scheme 8. Oxidation of styrylcarbazole 19 with HBr/DMSO mixture under milder condition to 1,2-diketones.

well as acceptable yields. Subsequently, this group[100] used HBr-
DMSO reagent to convert the styrylcarbazole 19 into benzil
derivative 20. During the oxidation of alkene, tandem bromina-
tion at benzene ring was also observed to form 1(6-bromo-9-
methylcarbazol-4-yl)-2-phenylethan1,2-dione 21 (Scheme 8).
The activity of styrylcarbazole in this reaction is governed
by electron donating properties of 3-carbazolyl substituents
relative to the benzene ring. Carbazole with π-electron
abundance is responsible for the bromination at 6th position.
On increasing the temperature of the reaction by 80 °C, pure
benzil derivative was formed in 47% yield and further increase
in the temperature to 120 °C resulted into the mixture of
products one of that 22 is shown in the Scheme 8.
Also, previously the oxidation of diarylalkynes using iodine
with DMSO by Filimonov et al. has been discussed earlier.[73]
Similarly, they devised another system for oxidation of stilbene
derivatives 23 employing iodine with DMSO at 155 °C to the
corresponding benzils 24 with approximately 85% yields
(Scheme 9).
An expedient, highly chemoselective green chemical ap-
proach for the conversion of diarylalkens 25 to respective benzil
26 by I2/H2O in absence of acid or metal under air to oxidize has
been reported.[101] After optimization it was observed that the
trans-stilbene gave 96% yield of benzil in presence of two
equivalents of iodine (iodine-water system) at 140 °C for 20 h
under air (Scheme 10). To check the scalability of the present
method, even a gram-scale reaction preceded well, giving the
desired benzil 26 in 81% yields under the optimized conditions.
Mechanism for the formation of benzil under the influence of I2/
H2O involves the steps shown in the Scheme 10a below.
Fortunately, it was found that the electronic properties, the
steric hindrance of the substituents on the benzene rings and
use of the cis or trans-isomer have no significant influence on
the reactivity. Obviously, almost all substituted trans-stilbenes
25 were converted to their corresponding benzil 26 in high
yields (88–98%). On the other hand, the cis-stilbenes 25 could
be smoothly transformed into the desired benzil products 26 in
excellent yields under the optimal reaction conditions (95–
96%). Internal alkenes substituted with aliphatic groups or
heteroaromatic rings did not convert well under these reaction
conditions (Table 6). Furthermore, alkenes which were tri-
substituted at the C=C bond were also found to be inert.
Table 6. I2/H2O catalyzed oxidation of alkenes.
Entry No. Ar Ar’ Yield [%]

26 a phenyl phenyl 96
26 b p-tolyl phenyl 94
26 c m-tolyl phenyl 97
Table 5. Preparation of benzils 18 from stilbenes 17 using HBr and DMSO
26 d o-anisyl phenyl 97
system.
26 e p-anisyl phenyl 56
Entry No. Ar1 Amount of HBr [ml] Yield [%] 26 f p-chlorophenyl phenyl 96
26 g m-chlorophenyl phenyl 98
18 a phenyl 1.0 86 26 h o-chlorophenyl phenyl 91
18 b p-tolyl 1.0 80 26 i p-bromophenyl phenyl 89
18 d p-bromophenyl 0.50 78 26 j m-bromophenyl phenyl 92
18 e p-anisyl 1.0 84 26 k o-bromophenyl phenyl 88
18 f p-nitrophenyl 2.5 56 26 l 2,4-dichlorophenyl phenyl 78
26 m 2,6-dichlorophenyl phenyl 51
26 n 1-Napthyl phenyl 90
26 o p-fluorophenyl phenyl 98
26 p p-trifluoromethylphenyl phenyl 91
26 q p-chlorophenyl p-tolyl 96
26 r p-chlorophenyl m-tolyl 96
26 s p-chlorophenyl p-anisyl 95
26 t p-chlorophenyl p-fluorophenyl 93
26 u p-chlorophenyl p-bromophenyl 49
26 v p-chlorophenyl m-chlorophenyl 97
26 w p-chlorophenyl o-trifluoromethyl 45
26 x phenyl p-tolyl 95
Scheme 9. Iodine-DMSO mediated oxidation of stilbene 23 to correspond- 26 y phenyl p-chlorophenyl 96
ing benzils 24. 26 z phenyl p-fluorophenyl 96

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Scheme 10. Oxidation of stilbenes 25 in an I2/H2O system for synthesis of benzil 26. a) Plausible mechanism for the oxidation of stilbenes in an I2/H2O system
under aerobic conditions.

Table 7. Percentage yield of benzil 1 in presence of various fluorinated

The plausible mechanism involves the initial formation of alcohols in presence of MEC-31 or Selectfluor.
iodonium ion A followed by sequence of steps. The second step Entry ROH Electrophilic Reaction Yield [%] of
of the reaction is the attack of water on one of carbon of the No. Reagent Temperature/ Benzil 1
iodonium ion A, resulting in the ring opened product B. Time
Tentatively, benzil derivatives 26 could be directly derived from 28 a CF3CH2OH MEC-31 25 °C, 48 h 14
the oxidation of B with iodine in water under air. On the other 28 a CF3CH2OH Selectfluor 60 °C, 48 h 09
28 a CF3CH2OH MEC-31 60 °C, 48 h 21
hand, the subsequent replacement reaction could be easily
28 b CH2FCH2OH MEC-31 60 °C, 48 h 25
achieved by the attack of water to provide the corresponding 28 c CF3CF2CH2OH MEC-31 60 °C, 48 h 35
diol C. The benzil derivative 26 is also obtained from C by 28 d CHF2(CF2)3CH2OH MEC-31 60 °C, 48 h 48
28 e (CF3)2CHOH MEC-31 60 °C, 48 h 52
reaction with I2/H2O/O2. Water also participates in the trans-
28 f (CF3)3COH MEC-31 60 °C, 48 h 90
formation of stilbenes 25 to benzils 26 as evidenced by isotopic
labelling experiments. For example, when the oxidation reac-
tion was performed in presence of H2O18 (97%), O18 labelled
benzils 26 were obtained. A broad range of substituted slightly. In presence of MEC-31 at 60 °C for 24 h, the yield of the
stilbenes 25 was examined in order to assess the applicability α-keto ether 28 was found to be higher. The yields of the α-
and scope of the system, and the results are summarized in keto ether 28 and benzil 1 were found to be a function of the
Table 6. extent of fluorination of the alcohols 27 a used. Under similar
1-(Chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]- reaction conditions, various fluorinated alcohols 27 b–f were
octanebis(tetrafluoroborate) (Selectfluor) and N,N-difluoro-2,2’- converted into the corresponding α-keto ethers 28 b–f in
bipyridiniumbis(tetrafluoroborate) (MEC-31) are well-known moderate to good yields (Scheme 11, Table 7). Interestingly,
electrophilic reagents that are effective in introducing fluorine perfluoro-tert-butyl alcohol 27 f produced mostly benzil 1 in
into an organic molecules.[102a–b] In view of this, Manandhar and 90% yields and a trace of α-keto ether 28 f was detected by GC/
co workers[103] treated trans-stilbene 16 with Selectfluor in MS.
trifluoroethanol 27 to obtain α-keto ether 28 as the major The oxygen can be incorporated into organic substrates
product and benzil 1 as minor product at 25 °C. However, both using oxidation or hydration transformations and are commonly
of these were formed in low yields (Table 7). performed using transition-metal-based catalysts. These are
Even after increasing the temperature of the reaction expensive, difficult to remove, toxic, and are frequently
mixture to 60 °C for 48 h, the yield of 28 and 1 improved only obtained from limited natural resources. As such, the search for

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Scheme 11. Synthesis of benzil 1 in presence of electrophilic fluorinating reagents.
a catalyst that combines the toxicological benefits of a metal-
free synthesis with the convenience of heterogeneous workup,
whilst retaining high activity, is a continuing effort of critical
importance. In view of these facts, Bielawski et al. reported the
use of graphene oxide (GO), a readily available and inexpensive
material, as a mild and efficient carbon catalyst for the
generation of benzil from various alkenes and this process is
referred as “Carbocatalysis”. GO has been impregnated with
palladium nanoparticles that have very high turnover frequen-
cies in Suzuki-Miyaura coupling reactions.[104]
The propensity of GO to oxidize various alcohols prompted
Bielawski et al.[105] to explore the ability of this catalyst to oxidize
cis-stilbene. As shown in Scheme 12, benzil 1 was isolated in
49% yield after 24 hours at 100 °C by the treatment of cis-
stilbene 29 under the optimized conditions; no benzoin or
other oxidation products were observed in the crude reaction
mixture. The aromatic substituents, combined with a cis-
geometry, appear to be necessary to facilitate oxidation as
either isomerization or no reaction was observed when trans-
stilbene was explored as substrate under similar conditions
(Scheme 12). This apparent limitation may be due to steric
constraints or to the orientation of the interaction involved
between the olefins and the surface of the catalyst.[106] It is
interesting to mention here that the 1,2-dihydroxy-1,2-diphen-
yl-ethane was oxidized using GO to the corresponding benzil
wherein 96% conversion efficiency was observed.
To enhance the efficiency of the organic synthetic proce-
dures, combining the multiple steps without isolating any
Scheme 12. Oxidations of olefin 29 to benzil 1 using GO.
Scheme 13. Integrated electrochemical-chemical oxidation of diarylalkenes 25.
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intermediates is effective way.[107] Hence, it is useful to integrate
chemical reactions such as the generation of unstable highly
reactive species that are swiftly utilized for a further reaction
before they decompose.[108] In addition to chemical reactions
using chemical reagents and/ or catalysts, electrochemical
reactions using electron transfer on the surface of the electrode
serve as a powerful means of generating highly reactive species.
Hence, electrochemistry is of the immense help for the selective
introduction and removal of electrons under milder conditions.
In view of this, Ashikari et al.[109] envisaged that integration
of electrochemical oxidation and chemical oxidation would be a
nice approach to this challenge. Hence they reported an
example of such integration that is mediated by an unstable
reactive intermediate. Treatment of alkoxysulphonium cations
with a base such as triethylamine eventually gave the
corresponding benzils 30 in moderate to good yields
(Scheme 13). Hence, in this work, they chose to use alkoxysul-
phonium cations as key intermediates as mildest method for
oxidation of organic compounds. Although alkoxysulphonium
cations can be generated by several chemical methods, the
oxidation state of the precursors (RR’CHX; X = heteroatom) and
the resulting alkoxysulphonium cations (RR’CH-OS + Me2) are the
same, and the overall reaction to give RR’C=O is a two-electron
oxidation. If substrates of lower oxidation state, for example
RR’CH2, could be used to generate alkoxysulphonium cations,
the overall reaction would be a four-electron oxidation, and the
method would serve as a highly useful way of oxidizing organic
compounds. Electrochemical oxidation serves as a powerful
© 2021 Wiley-VCH GmbH
 Review
method for generating carbocations and onium ions under the Formation of cyclic 1,2-diketones using Ruthenium
mild condition.[110] Hence, Ashikari et al. have developed an prompted Chen et al. to convert the open chain 1,2-diary-
effective method for generating and accumulating carbocations lalkenes 25 into the corresponding benzil derivatives 33.[116a]
or onium ions by low-temperature electrochemical oxidation. Optimized reaction conditions viz., [Ru(cymene)Cl2]2 (1 mol%),
The method, which is called the “cation pool” method, has Bu4NI (30 mol%), t-BuOOH (3.6 equiv, 70% in aqueous solution)
been successfully applied to N-acyliminium ions,[111] alkoxycar- in toluene/MeCN/H2O at room temperature for 1 h furnished
benium ions[112] and diarylcarbenium ions.[113] benzil derivatives 33 in moderate to excellent yields
On the basis of these backgrounds, they envisaged that (Scheme 15).
carbocations generated by the cation pool method could be To show the utility of this expedient mild and chemo-
used for a subsequent reaction with DMSO to generate selective oxidation process the authors have analysed this
alkoxysulphonium cations, which would then react with an reaction in the synthesis of 35, an intermediate for the anti-
amine base to give the corresponding benzil compounds 30. In inflammatory drug. It was formed in moderate yield
addition, the electrochemical method also often suffers from (Scheme 16). The earlier reported methods required three steps
over oxidation. For example, anodic oxidation of alkenes[114a–b] for the preparation of compound 35.[116b]
and of 1,2-diols[114c] and their derivatives often leads to carbon- Investigation of reaction mechanism revealed that forma-
carbon bond cleavage. The present electrochemical method tion of benzoin as the intermediate which underwent oxidation
overcomes this unusual problem by integrating with an to form the benzil derivatives proposed as Scheme 16a. A cis-
extremely mild chemical method such as DMSO oxidation. dioxoruthenium intermediate A is formed initially from ruthe-
Therefore this method serves as a powerful and highly selective nium catalyst with TBHP which is followed by a [3 + 2] cyclo-
method for the conversion of stilbenes 25 to benzils 30 addition between intermediate A and the alkene 25. This
(Table 8). reaction generates intermediate B. The nucleophilic attack of
Khan et al. had reported the conversion of 1,2-di-halonor- iodide on ruthenium of intermediate B affords intermediate C.
bornenes 31 into α-diketones of norbornanes 32 under the β-hydrogen elimination from intermediate C leads to α-
influence of catalytic amount of Ru(III)chloride, NaIO4 and hydroxyl ketone D. The subsequent oxidation of D would
aqueous acetonitrile (6 : 1) (Scheme 14).[115] produce the desired benzil derivative 33. Lastly, oxidation of
the resulting Ru(II) species facilitated by TBHP formed cis-
dioxoruthenium intermediate A, completing the cycle.
Table 8. Integrated electrochemical-chemical oxidation of styrene deriva- Generally, alkenes with electron-donating substituents pro-
tives. vided the corresponding products in higher yield than those
Entry No. Ar Ar’ Electricity Yield bearing electron-withdrawing substituents. Both trans- and cis-
[F/mol] [%] alkenes were successfully transformed into corresponding
30 a p-chlorophenyl p-chlorophenyl 2.1 83 benzils derivatives for example 33 c, 33 i, 33 r, 33 u and 33 x. The
30 b phenyl phenyl 2.1 70 substrate scope showed the formation of following benzil
30 c phenyl p-cyanophenyl 2.1 50 derivatives 33 along with their yields is shown in Table 9.
30 d p-tolyl p-tolyl 2.1 71
While exploring the oxidising activity of selenium dioxide
(SeO2) for various organic substrates, Riley et al.[117] in the year
1935 first investigated the oxidising property of SeO2 for
diarylalkenes (stilbenes) to get benzils. The reaction was carried
out at elevated temperatures to get good yields. However,
Nagarkar et al.[118] made the investigation over the use of arene
diazonium salts 36 and styrene 37 in presence of catalytic
amount of Pd(OAc)2 and SeO2 for the one pot synthesis of
benzil derivatives 38 (Scheme 17). The reaction gave moderate
to appreciable yields with SeO2 which turned out to be a milder
reagent for the chemoselective synthesis of benzils 38.
The mechanism involves Heck-Matsuda reaction which
Scheme 14. Ruthenium-catalyzed oxidation of the tetrahalonorbornyl deriv-
proceeds by the formation of palladium cationic complex i. The
atives 31.
oxidative addition of arene diazonium salt 36 to Pd(OAc)2 by
the release of nitrogen gas. The cationic palladium complex
was reacted with styrene to intermediate ii which on β-hydride
elimination gives stilbene iii. Stilbene & palladium hydride
cationic complex coordinates as the entire electron density
shifted towards the metal to form iv. Further stilbene reacts
with palladium selenium intermediate v, followed by β-hydride
elimination leading to vi. The intermediate vii occurs by
Scheme 15. Ruthenium-catalyzed diarylalkenes 25 oxidation to benzil de- intramolecular transfer of oxygen takes place via closure of
rivatives 33. selenine and further on reductive elimination gives viii, which

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Scheme 16. Synthetic application of Ru-catalyzed oxidation as intermediate for preparation of imidazole-based selectin inhibitors 35. a) Plausible catalytic
cycle for Ru-catalyzed oxidation.
on expulsion of selenium gives benzil 38 (Scheme 17a). The
reaction yields were optimised when the substrates containing
electron donating substituent at the para position of the arene
diazonium salt gave higher yields but when NO2 group present
at meta position, yield of the benzils decreases and the
substrate scopes are summarized in Table 10.
3.4. Oxidation of 1,3-diketones
1,3-Diketones represent one of the most important class of
organic compounds, since they are applied as key structural
blocks in organic syntheses, exhibit different kinds of biological
activities, and display a broad range of ionophoric properties.
The 1,3-diketones have been used as substrates for the
construction of heterocycles[119] and also in the synthesis of 1,2-
diketones by degradation as discussed below in Scheme 18.
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Itoh et al.[120] developed a catalytic protocol for the direct
synthesis of benzils 41 from 1,3-diaryldiketones 40. 1,3-
Diketones with aryl groups at 1,3-position were degraded to
benzil derivatives 41 using iodide and base upon irradiation of
fluorescent light. In this regard, diaroyl methane was subjected
to iodine/Ca(OH)2 catalyzed aerobic photo-oxidation under
visible-light irradiation of fluorescent lamp to obtain benzil 41
(Scheme 19).
Analyses of scope and limitation for the oxidative synthesis
of benzils 41 indicated that they were obtained in good yields
regardless of an electron-donating or electron-withdrawing
group at benzene ring. Also, the proposed mechanism
indicated that the reaction occurs through the formation of
triketone (Table 11). The plausible mechanism has been
proposed in the Scheme 19a which involves the initial oxidation
under the influence of light in oxygen which gave a 1,3-
disubstituted propanetrione v. This further undergoes benzilic
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 Review

Table 9. Optimization of the substrate scope for the Ru-catalyzed oxidant.[121] The selective cleavage of the C C bond of 1,3-
oxidation. diaryldiketones 40 affords the benzil derivatives 42 in good
Entry No. Ar Ar’ Yield [%] yields under mild reaction conditions, which provides an
alternative for accessing the useful benzils (Scheme 20).
33 a phenyl phenyl 91
33 b phenyl p-tolyl 87 The scope of this transformation indicated that the reaction
33 c phenyl m-tolyl 86 of unsymmetrical 1,3-diketones was highly selective. Both
33 d phenyl p-chlorophenyl 82 electron-donating and electron-withdrawing substituents in the
33 e phenyl p-fluorophenyl 84
33 f phenyl p-anisyl 86 aryl ring of 1,3-diaryldiketones 40 tolerated the reaction
33 g phenyl o-fluorophenyl 71 conditions well to give the corresponding 1,2-diketones in
33 h phenyl E-methyl-phenylacrylate 49 good yields. In addition, the steric hindrance on aryl ring played
33 i phenyl m-chlorophenyl 74
33 j phenyl p-bromophenyl 79 little role in the reaction and 2- and 1-naphthyl-substituted 1,3-
33 k phenyl p-bromophenyl 73 diketones underwent the transformation smoothly to afford the
33 l phenyl p-acetylphenyl 67 corresponding benzils 42 in good yields (Table 12).
33 m phenyl p-trifluoromethyl 63
33 n 1-methylindoline – 83 A plausible reaction mechanism (Scheme 20a) indicates the
33 o phenyl thiophenyl 78 radical reaction of 1,3-diaryldiketones 40 in the presence of TBN
33 p phenyl furyl 44 produces the diketone oxime A which is possibly converted to
33 q phenyl propyl 62
33 r phenyl o-chlorophenyl 73 intermediate B in the presence of TBN without the use of iron
33 s p-cyanophenyl p-anisyl 71 chloride. The release of N2O from intermediate B gives the
33 t phenyl o-anisyl 88 triketone C under the reaction conditions in situ. Then the iron
33 u undecyl propyl 71
33 v phenyl cyclohexyl 72 chloride coordinates with the carbonyl of intermediate C to
33 w phenyl p-acetoxyphenyl 65 form intermediate D, which undergoes a 1,2-Wagner-Meerwein-
33 x phenyl isobutyl 75 type rearrangement of a benzoyl group with an electron pair to
33 y phenyl N-acetamidophenyl 90
33 z phenyl phenylpropynyl 46 the electrophilic carbon resulting in the intermediate E. The
subsequent (or simultaneous) liberation of carbon monoxide of
intermediate E results in the benzil products 42.
Table 10. Reaction yields for the chemoselective oxidation of styrene 37 Yuan et al. reported a method for the preparation of benzil
to benzils 38. derivatives 43 by oxidative cleavage of 1,3-diaryldiketones 40
Entry No. Ar Ar’ Yield [%] with DMSO catalyzed by iodine.[122] A pilot reaction with the
dibenzoylmethane with iodine (1.0 equiv) at 150 °C in DMSO
38 a phenyl phenyl 90
38 b phenyl p-tolyl 92 under an oxygen atmosphere gave the corresponding benzils
38 c phenyl p-anisyl 95 43 in 76% yields. The oxidative cleavage of various substituted
38 d phenyl p-chlorophenyl 88
1,3-diaryldiketones was obtained by iodine (2.5 mol %) in DMSO
38 e phenyl p-bromophenyl 85
38 f phenyl m-nitrophenyl 56 at 150 °C in air (Scheme 21). Furthermore, 1,3-diaryl diketones
38 g phenyl 3,4-dichlorophenyl 72 40 bearing both electron-donating and electron-withdrawing
38 h p-tolyl p-bromophenyl 88
groups on each aromatic ring could be converted into the
38 i p-tolyl p-anisyl 94
38 j p-tolyl p-chlorophenyl 90 corresponding 1,2-diaryldiketones 43 in good yields under the
38 k m-anisyl p-chlorophenyl 43 optimised conditions. However, electron-withdrawing groups
38 l p-tolyl 1-methoxy-4-methylphenyl 75
38 m p-anisyl p-anisyl 96
38 n p-bromophenyl o-chlorophenyl 77
38 o p-bromophenyl p-tolyl 92
38 p 2-pyridyl p-anisyl 62 Table 12. Iron-promoted selective C C bond cleavage of 1,3-diaryldike-
tones.
Entry No. Ar Ar’ Yield [%]
Table 11. Optimization of substrate scope for benzil derivative 41.
42 a phenyl phenyl 80
Entry No. Ar Ar’ Yield [%] 42 b p-anisyl phenyl 80
42 c p-tolyl phenyl 70
41 a phenyl phenyl 72 42 d m-tolyl phenyl 71
41 b p-anisyl phenyl 56 42 e o-tolyl phenyl 83
41 c p-tert-butylphenyl phenyl 64 42 f p-fluorophenyl phenyl 72
41 d p-tolyl phenyl 62 42 g p-chlorophenyl phenyl 76
41 e o-tolyl phenyl 60 42 h p-bromophenyl phenyl 76
41 f p-nitrophenyl phenyl 66 42 i o-bromophenyl phenyl 70
42 j p-iodophenyl phenyl 70
42 k 2-naphthyl phenyl 70
42 l 1-naphthyl phenyl 78
acid type rearrangement to give 2-hydroxy-3-oxo-2,3-disubsti- 42 m pyrazol-2-yl phenyl 60
tuted-propanoic acid viii. This was further converted into the 42 n thien-2-yl phenyl 65
42 o furan-2-yl phenyl 45
benzil derivative 41 by oxidative decarboxylation. 42 p furan-2-yl thien-2-yl 68
Zhang et al. proposed the iron-promoted C C bond cleav- 42 q furan-2-yl pyrazol-2-yl 45
age of 1,3-diketones in presence of tert-butyl nitrite (TBN) 42 r thien-2-yl thien-2-yl 84

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Scheme 17. One-pot chemoselective oxidation of styrene 37 using Pd(OAc)2/SeO2. a) Plausible mechanism for oxidation of styrene 37 under milder reaction
condition.
Scheme 18. Oxidation of 1,3-diketones 39 to benzil 1.
on both aromatic rings led to a decreased yield depicted in
Table 13.
The mechanism of 1,2-diaryldiketone formation from 1,3-
diaryldiketone 40 (Scheme 21a) involved the reaction of
compound 40 which reacted with iodine to form the 2-iodo
derivative in DMSO, which was oxidized by DMSO to obtain the
triketone via the sulfonium salt. At the same time, hydrogen
iodide was generated in the system. The triketone was easily
converted into key intermediate iii by the effects of a small
amount of water. Intermediate iv was formed by a reverse
benzilic acid rearrangement in the presence of hydrogen iodide.
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On the other hand, hydrogen iodide could be oxidized by
DMSO to regenerate iodine, which can once again be used for
the first stage. Then, final benzil product 43 can be generated
when intermediate iv undergoes oxidative decarboxylation in
the presence of iodine.
Looking into the significance of the transformations of 1,3-
diaryldiketone into benzils, Jiao et al. developed a copper-
catalyzed C C bond cleavage of 1,3-diaryldiketones to synthe-
size benzils using molecular oxygen as oxidant.[123] The reaction
of 1,3-diphenylpropane-1,3-dione 40 in presence of CuBr
afforded the benzil 44 in 51% yield under molecular oxygen
conditions (Scheme 22). The aromatic ring of 1,3-diketones
derivatives was found to be tolerant of both electron-rich and
electron deficient groups. However, aliphatic 1,3-diketones do
not work under this condition (Table 14).
The proposed mechanism is shown in Scheme 22a. Under
molecular oxygen conditions, copper (I) was initially oxidized to
copper (II). Then, the key intermediate A was produced from 40
via copper-catalyzed aerobic oxidative process. Subsequently,
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 Review

Scheme 19. One-pot synthesis of benzils 41 by aerobic photo-oxidation. Scheme 19a. Plausible path for the conversion of 1,3-diaryldiketones 40 to benzils
41.

the key intermediate A coordinated and activated by copper (II) TEMPO (2,2,6,6-Tetramethylpiperidine oxide) a mild oxidant
underwent a 1,2-Wagner-Meerwein-type rearrangement to afford has been used in the preparation of carbonyl compounds,
the intermediate B. Finally, the C C bond cleavage released imines, nitriles by oxidising alcohols, amines respectively in
carbon monoxide and gave 44 as the terminal product. preparative as well as industrial scale.[124] TEMPO is also
employed in the radical reaction, C C bond formation and C H
functionalization. Apropos, Zou et al.[125] utilized the TEMPO-
mediated mild oxidation (10 mol %) of 1,3-dicarbonyl com-
Table 13. Reaction yields of benzil derivatives 43 by oxidative cleavage of
1,3-diaryldiketones 40 substrates by I2/DMSO. pound 40 in presence of CuBr. After screening the different
solvents using various copper salts at varied temperature, the
Entry No. Ar Ar’ Yield [%]
optimized condition was combination of 40 (1 equiv), TEMPO
43 a phenyl phenyl 97 (2 equiv) and CuBr (0.10 equiv) in AcOH for 2 h at 100 °C
43 b phenyl m-anisyl 85
43 c phenyl p-anisyl 92 (Scheme 23) for the formation of benzils 45.
43 d phenyl p-tolyl 95 1,3-Diketones with the substituents bearing electron-donat-
43 e phenyl o-anisyl 73 ing groups on phenyl ring underwent transformation in good
43 f phenyl p-chlorophenyl 80
43 g phenyl m-fluorophenyl 94 yields. Thus, electronic withdrawing inductive effect played a
43 h o-anisyl p-tolyl 72 significant role during transformation. The heteroaryl 1,3-
43 i p-tolyl p-anisyl 90 diketones were obtained in varying yields. Substituents with
43 j p-tolyl p-tolyl 84
43 k m-fluorophenyl p-anisyl 86 one or two electron-donating heteroaryls such as thienyl and
43 l m-fluorophenyl p-tolyl 93 furyl group gave 45 q, 45 r and 45 s in 82%, 88% and 85% yields
43 m p-chlorophenyl p-chlorophenyl 57 respectively. However, one electron-withdrawing substituted

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Scheme 20. Iron-Promoted C C Bond Cleavage of 1,3-diaryldiketones 40 to benzils 42. a) Proposed reaction mechanism for C C bond cleavage of 1,3-
diketones.

Table 14. Synthesis of 1,2-diketones from 1,3-diketones via aerobic removal of 2,2,6,6-tetramethylpiperidine D, and the correspond-
oxidative C C bond cleavage process.
ing Cu + 2 could coordinate with C to form complex E, which
Entry No. Ar Ar’ Yield [%] underwent a 1,2-Wagner-Meerwein-type rearrangement to form
44 a phenyl phenyl 51 the intermediate F. The simultaneous elimination of carbon
44 b p-tolyl p-tolyl 49 monoxide from F resulted in the formation of benzil 45.
44 c p-anisyl p-anisyl 56
44 d 3,4-dimethylphenyl 3,4-dimethylphenyl 46 Zhu and coworkers reported the conversion of 1,3-diaryl-2-
44 e p-tert-butylphenyl p-tert-butylphenyl 56 diazo-1,3-diketones 46 to 1,2-diaryl-1,2-diketones (benzils) 47
44 f p-fluorophenyl p-fluorophenyl 46 based on a rhodium(II)-catalyzed aerobic decomposition
44 g p-chlorophenyl p-chlorophenyl 45
44 h p-trifluoromethylphenyl p-trifluoromethylphenyl 41 process.[126] The reaction occurs at ambient temperatures and
44 i 3-thienyl 3-thienyl 45 was found to be catalyzed by few dirhodium carboxylates
44 j 2-naphthyl 2-naphthyl 42 (5 mol%) under balloon pressure of oxygen. By this newly
44 k phenyl p-trifluoromethylphenyl 46
44 l phenyl p-anisyl 42 developed strategy, a large array of benzil derivatives 47 were
synthesized from the corresponding diazo substrates displaying
varying yields. Mechanistically, it was proposed that the
decomposition may proceed via the interaction of a ketene
heteroaryls viz., pyridyl gave the low yields of products 45 t intermediate resulting from a Wolff rearrangement of the
(46%) and 45 u (51%) (Table 15). carbenoid, with a rhodium peroxide or peroxy radical species
A plausible mechanism (Scheme 23a) outlined, shows that generated upon the activation of molecular oxygen
initially TEMPO abstracts a hydrogen atom from α-methylene of (Scheme 24). The reactions with Rh2(OAc)4 offered the desirable
1,3-diketone 40 to generate sp3-carbon radical A, which was products in moderate yields. Also, substrates containing m-NO2-
then trapped by another molecule of TEMPO to produce or p-CF3 substituent were found to give the products in much
intermediate B, the fragile N O bond was broken easily in the better yields than those obtained from methoxy-substituted
presence of copper salt. Triketone C was formed as a result of counterparts. A naphthyl ring was expected to exert more steric

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Scheme 21. Oxidative cleavage of 1,3-diaryldiketones 40 to benzils 43. a) Possible reaction pathway for oxidative cleavage of 1,3-diketones 40.

Table 15. Optimization of the substrate scope of 1,3-diketones 40 to form

benzils 45. repulsion than a phenyl group within a ketene structure, which
Entry No. Ar Ar’ Yield [%] accounts for the lower yields shown in Table 16.
On probing the reaction conditions, it was found that
45 a phenyl phenyl 90
45 b p-tolyl phenyl 81 gaseous oxygen or O2 in the air with the combination of the
45 c o-tolyl phenyl 85 catalyst was possibly serving as a reagent for producing
45 d p-anisyl phenyl 88 corresponding benzils. As the critical roles of oxygen and
45 e p-tolyl p-tolyl 80
45 f o-tolyl o-tolyl 84 catalyst results in the generation of 47, hence looking into
45 g p-anisyl p-anisyl 86 sequences of the trials, a mechanistic approach was proposed
45 h o-anisyl o-anisyl 63 via the trione intermediate but it was ruled out further. On
45 i p-chlorophenyl phenyl 82
45 j p-bromophenyl phenyl 80 closer inspection it was implied that 47 was also possibly
45 k o-bromophenyl phenyl 80 derived from the ketene intermediate (Scheme 24a). The
45 l p-bromophenyl p-bromophenyl 52 dirhodium(II) catalyst (RhLn) was partially oxidized to a rhodium
45 m o-bromophenyl o-bromophenyl 65
45 n p-anisyl p-bromophenyl 91
peroxide or peroxy radical complex upon exposure to oxygen,
which were assigned as cat-O2 (Rh26 + or Rh4 +) and cat-O2
*

45 o p-nitrophenyl phenyl 74
45 q phenyl 2-thienyl 82 (Rh25 + or Rh3 +), tentatively (Scheme 24a). The non-oxidized
45 r phenyl 2-furanyl 88
45 s 2-thienyl 2-thienyl 85
catalyst converts 46 to A, which then undergoes a Wolff
45 t phenyl 2-pyridyl 46 rearrangement to afford a ketene C. The C=C double bond of C
45 u 2-pyridyl 2-thienyl 81 coordinates with cat-O2 and further inserts into the rhodium-
dioxygen bond, yielding a five-membered peroxometallocycle
D (pathway A).

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Scheme 22. Copper-Catalyzed Aerobic Oxidative C C bond cleavage of 1,3-Diaryldiketones. a) Plausible mechanism of the transformation.

Table 16. Preparation of benzils 47 by Rhodium-catalyzed aerobic decom-

position. gets directly engaged in a cycloaddition with O2 to produce
Entry No. Ar Ar’ Yield [%] cyclic peroxide E and benzil 47 (pathway B).
After the use of single catalyst in an routine oxidative
47 a 2’-biphenyl phenyl 47/43
47 b phenyl phenyl 82 degradation of 1,3-diaryldiketones, cocatalyst were explored for
47 c o-tolyl phenyl 40/51 the synthesis of benzils derivatives by Chen and co-workers.[127]
47 d o-chlorophenyl phenyl 63
Copper/Iodine-cocatalyzed C C Cleavage of 1,3-diaryldiketones
47 e m-tolyl phenyl 74
47 f m-chlorophenyl phenyl 73 40 and the protocol was performed efficiently in DMSO as an
47 g m-anisyl phenyl 56 oxidant at elevated temperatures to higher yields of benzils 48
47 h m-nitrophenyl phenyl 72
(Scheme 25).
47 i 1’-biphenyl phenyl 77
47 j p-tolyl phenyl 71 Looking into the optimization results, the mechanism path-
47 k p-chlorophenyl phenyl 78 way (Scheme 25a) was predicted by CuBr coordinated with 1,3-
47 l p-anisyl phenyl 57
diaryldiketones 40 to form the enol-[Cu] complex i, which
47 m p-trifluoromethylphenyl phenyl 81
47 n benzo[d][1,3]-dioxol-5-yl phenyl 68 oxidative reacted with iodine by DMSO which gave 2-iodo-
47 o 2’-naphthyl phenyl 64 substituted 1,3-diketone-[Cu] complex ii. This replaces the
47 p m-anisyl p-tolyl 73
intermediate ii with DMSO to intermediate iii. The decomposi-
47 q m-nitrophenyl p-tolyl 78
47 r phenyl 3,5-dimethylphenyl 68 tion of the intermediate iii produces the 1,2,3-triketone-[Cu]
47 s phenyl p-acetylphenyl 83 complex intermediate iv, which sequentially undergoes intra-
molecular C C bond cleavage to generate the carbonyl cation
v. Subsequently, the decarbonylation of the intermediate v
It is also possible that D can be produced by a radical enhances the formation of benzils 48 and the CO expulsion.
addition of cat-O2 to C. In either way, the rhodium ion adds to Looking into the optimized conditions, the yields and
*

the central carbon rather than the terminal carbon of the
ketene minimizing the steric repulsion between the ligands (Ln)
and the aryl groups. Subsequent decomposition of D allows the
production of 57 along with complex B and the catalyst was
regenerated from B, as proposed in Scheme 24a. Also, ketene
substrate scopes were summed up to efficiently understand the
method reported. It was investigated that two symmetrical 1,3-
diaryldiketones smoothly delivered benzils in excellent yields,
whereas two non-symmetrical 1,3-ketones bearing an electron-

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Scheme 23. Catalytic transformation of 1,3-dicarbonyl compounds 40 to benzils 45. a) Plausible mechanism for the Copper-catalyzed TEMPO oxidative
cleavage of 1,3-diketones.
donating substituent were highly reactive to give benzils in
excellent yields to moderate yields (Table 17).
3.5. Oxidation of 1,2-diols
1,2-Diols or vicinal diol are the compounds in which the two
hydroxyl groups occupy vicinal positions, i. e., they are attached
to adjacent atoms. These compounds are also called glycols. On
commercial scales, 1,2-diols 51 were prepared by the hydrolysis
of epoxides 50 which intern were prepared by epoxidation of
the alkene 49 (Scheme 26).[128]
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These 1,2-diols 52 are easily available source for the
conversion into 1,2-diketones such as benzil derivatives 1
(Scheme 27). For example, efficient oxidation of 1,2-diphenyl-
diols to benzil has been reported by using various oxidizing
reagents such as aq. NaOCl,[129a] 4-MeO-TEMPO,[129b] (4-AcNH-
TEMPO)-OTs-TsOH,[129c] 4-PhCO2-TEMPO-electrolysis,[129d] n-Bu4N-
[MoO(O2)2(C5H4N(O)CO2)],[130] H2O2-[C5H5N-(CH2)15CH3]3{PO4 [W-
(O)(O2)2]4},[131a] and O2-Co(acac)3-N-hydroxyphthalimide.[131b]
The above mentioned methods were dedicated for the 1,2-
diketones including mainly the alkyl groups along with benzil 1
only. A simple and convenient procedure for the synthesis of a
various benzils 54 by the oxidation of corresponding 1,2-diols
53 with N-bromosuccinimide (NBS) in refluxing carbon tetra-
© 2021 Wiley-VCH GmbH

Scheme 24. Rh(II)-catalyzed aerobic decomposition of 1,3-diaryl-2-diazo-1,3-diketones 46 to benzils 47. a) Plausible reaction pathways to 47 via a ketene
intermediate formation.
chloride (80–85 °C) in the presence or absence of pyridine has
been reported by Khurana et al.[132] Various benzils 54 were
obtained in nearly quantitative yields by a simple work up
procedure (Scheme 28). The reaction was carried out with NBS
in presence of calcium carbonate, triethylamine and pyridine
(proton acceptors). The role of steric factor on the rate of the
reaction was analyzed by the reactions of pure meso- and dl-
hydrobenzoins, meso- and dl-4,4’-dichlorohydrobenzoins and
meso- and dl-4,4’-dimethylhydrobenzoins with NBS under
identical reaction conditions. It was observed that meso-hydro-
benzoins underwent oxidation faster than the corresponding
dl-isomers to give benzils as tabulated in Table 18.
The mechanism of oxidation of alcohols involved the
positive halogen as the attacking species and hence the 1,2-
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diols 53 react with NBS to form a hypobromite i which readily
loses hydrogen bromide to form the carbonyl product 54. The
oxidations were undoubtedly proceeding via the corresponding
acyloins and had been confirmed when the progress of various
reactions was monitored (Scheme 28a).
In the view of developing environmentally benign reaction
conditions such as low cost reagents, aqueous reaction
conditions, moderate temperatures and short reaction times,
Khurana and co-workers screened sodium bromate with
bmim[HSO4] as an oxidising agent.[133] NaBrO3:bmim[HSO4]
oxidized 1,2-diols 55, in aqueous medium into corresponding
benzils 56 in excellent yields (Scheme 29). The substrate scope
was exploited for the optimized conditions depicted in the
© 2021 Wiley-VCH GmbH
 Review

Scheme 25. CuBr/I2 cocatalyzed transformations of the 1,3-diaryldiketones 40. a) Plausible mechanism for the transformation of 1,3-diaryldiketones.

Table 17. Reaction yields and substrate scope for the transformations of
1,3-diaryldiketones. Table 19, whereas the recyclability of the ionic liquid however
Entry No. Ar Ar’ Yield [%] decreased the yields in fourth and fifth cycles.
The first successful methyltrioxorhenium catalyzed oxidation
48 a phenyl phenyl 94
48 b p-tolyl p-tolyl 90
of 1,2-diols 55 to the corresponding benzils 57 using hydrogen
48 c p-anisyl p-anisyl 92 peroxide as oxidant (Scheme 30) was reported by Sain et al.[134]
48 d phenyl p-tolyl 96 Benzil derivatives 57 were obtained when the 1,2-diols 55 were
48 e phenyl p-anisyl 94
48 f phenyl p-chlorophenyl 90
subjected to drop-wise addition of aqueous hydrogen peroxide
48 g phenyl p-carbmethoxyphenyl 86 (30%) in refluxing acetonitrile using methyltrioxorhenium as
48 h phenyl o-chlorophenyl 83 catalyst. Hydrobenzoins 55 underwent oxidation easily. Interest-
48 i p-tolyl p-chlorophenyl 89
48 j p-fluorophenyl p-chlorophenyl 91
ingly, those with the electron donating groups were found be
48 k p-fluorophenyl p-trifluoromethylphenyl 93 more active. The reaction was faster at elevated temperature
48 l phenyl thiophenyl 87 and water trapping reagent MgSO4 was also essential for the
48 m phenyl n-pentyl 80
48 n phenyl cyclopropyl 85
yield of the reaction (Table 20).
48 o phenyl t-butyl 90 An expedient method for the formation of benzil derivatives
48 p phenyl methyl trace 58 by Bromamine-T oxidation of 1,2-diols 55 using RuCl3 as
48 q phenyl methoxy 81
catalyst at alkaline pH has been reported[135] (Scheme 31).
Hydrobenzoin 55 in general was found to be more reactive
than aliphatic diols and required lesser reaction time for

Scheme 26. Synthesis of 1,2-Diols in water by epoxidation-hydration reactions.

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Scheme 27. Oxidation of 1,2-diols 52 to benzil 1. Scheme 29. Oxidation of 1,2-diols 55 to 1,2-diketones 56 with NaBrO3.

oxidation to benzil 58. Hydrobenzoins 55 containing electron- Table 19. Optimization for the substrate scope for oxidation of 1,2-diols
donating groups were by far the most reactive substrates. These 55 with NaBrO3.

results are summarized in Table 21. Entry No. Ar Ar’ Yield [%]
In continuation of finding a environmental benign methods 56 a phenyl phenyl 88
for the synthesis of benzil derivatives, Zhang et al. developed a 56 b p-chlorophenyl p-chlorophenyl 87
highly efficient and mild procedure using 2,2,6,6-tetrameth- 56 c p-anisyl p-anisyl 84
56 d p-tolyl p-tolyl 89
ylpiperidin-1-yloxy (TEMPO) as the catalyst.[136] The oxidation of 56 e m-chlorophenyl m-chlorophenyl 82
1,2-diols with iodobenzene dichloride as the stoichiometric 56 f p-bromophenyl p-bromophenyl 81
oxidant and pyridine as the base served corresponding benzils 56 g o-tolyl o-tolyl 78
56 h o-chlorophenyl o-chlorophenyl 80
in excellent yields (Scheme 32). 56 i o-bromophenyl o-bromophenyl 82
56 j o-anisyl o-anisyl 80
56 k p-fluorophenyl p-fluorophenyl 78
56 l n-butyl n-butyl 72
56 m n-octyl n-heptylic acid 78

Scheme 28. Synthesis of benzils 54 from 1,2-diols 53 using NBS in carbon tetrachloride. a) Plausible mechanism for the oxidation of 1,2-diols 53 via acyloins.

Table 18. Synthesis of 1,2-diol 53 with NBS in Pyridine to benzil 54.

1,2-Diol Ar Benzil Molar ratio [1,2-Diol + NBS + Pyridine]/time [hr] Yield [%]

53 a phenyl 54 a 1 : 2.5 : 0/2.5 94

53 b 4-chlorophenyl 54 b 1 : 3 : 0/2.75 96
53 c 2-chlorophenyl 54 c 1 : 3 : 0/2.00 82
53 d 4-bromophenyl 54 d 1 : 3 : 0/3.00 87
53 e 3-bromophenyl 54 e 1 : 3 : 0/1.75 37
53 f 1-naphthyl 54 f 1 : 3 : 0/3.00 82
53 g 2-naphthyl 54 g 1 : 3 : 0/2.75 97
53 a’ phenyl (diol is meso) 54 a’ 1 : 2.5 : 0/2.75 81
53 a’’ phenyl (diol is dl pair) 54 a’’ 1 : 2.5 : 0/1.25 93
53 b’ p-chlorophenyl (diol is meso) 54 b’ 1 : 3 : 0/1.50 82
53 b’’ p-chlorophenyl (diol is dl pair) 54 b’’ 1 : 3 : 0/3.00 82
53 h p-tolyl 54 h 1 : 3 : 1/1.75 83
53 h’ p-tolyl (diol is meso) 54 h’ 1 : 3 : 1/1.25 77
53 h’’ p-tolyl (diol is dl pair) 54 h’’ 1 : 3 : 1/1.75 71
53 i o-tolyl 54 i 1 : 3 : 5/2.50 72
53 j o-anisyl 54 j 1 : 3 : 2/1.50 83

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4. Carbon-Carbon Bond Forming Reactions

Carbon-carbon bond forming reactions are important ones

since they are used in the production of many commercially
important synthetic molecules such as pharmaceuticals, dyes,
and plastics. Aldol reactions, Friedel-Craft’s alkylation, acylation,
Scheme 30. CH3ReO3-catalyzed oxidation of 1,2-diols 55 using H2O2 as Diels-Alder reaction, the reaction of Grignard reagent or alkyl/
oxidant. aryl lithium to a carbonyl group, a Heck reaction, a Michael
reaction and a Wittig reaction are the common reactions of the
carbon-carbon bond forming reactions. Under the influence of
Table 20. 1,2-Diol oxidation with CH3ReO3/H2O2 in acetonitrile into benzils transition metal catalysts or Lewis acids the carbon-carbon
57.
formations can be carried out. As discussed in the above
Entry No. Ar Ar’ Yield [%] sections, conventional oxidation of benzoin, alkenes or alkynes
57 a phenyl phenyl 92 are established methods for the formation of benzils. In
57 b p-anisyl p-anisyl 95 addition to these, benzil derivatives have also been reported via
57 c p-tolyl p-tolyl 94
57 d p-anisyl phenyl 92 the carbon-carbon bond forming reactions as discussed below.
57 e p-chlorophenyl p-chlorophenyl 92 Benzoin is one of the cheap sources for the formation of
57 f p-N,N-dimethylphenyl p-N,N-dimethylphenyl 94 benzil derivatives. But, benzoin condensation is not possible for
57 g 2-furyl 2-furyl 97
57 h o-chlorophenyl o-chlorophenyl 90 the aromatic aldehydes containing electron donating groups
57 i p-nitrophenyl p-nitrophenyl 85 such as N,N-dimethyl groups and hence this restricts the
57 j o,o’-chlorophenyl o,o’-chlorophenyl 80 formation of benzoin containing electron-donating groups at
para-positions of phenyl rings. Therefore, benzils containing
N,N-dimethyl groups cannot be obtained by the above
methods. This has been overcome by the use of oxalylchloride
as it acts readily as an acylating agent. Hence, 4,4’-bis(dimeth-
ylamino)benzil 61 has been prepared by heating a mixture of
N,N-dimethylaniline 60 and oxalyl chloride in presence of
anhydrous aluminium chloride suspended in carbon disulphide
Scheme 33.[137]
Scheme 31. Bromamine-T mediated RuCl3 catalyzed oxidation of 1,2-diols Conversely, Girard et al. coupled two acyl groups of acid
55 to benzil 58.
chlorides 62 by carbon-carbon formation bond using the
reducing agents. For example, SmI2 and YbI2 exhibit very good
Table 21. Oxidation of 1,2-diols with Bromamine-T using RuCl3.xH2O as
reducing properties in THF solution.[138] Therefore when the acid
catalyst. chloride 62 was added to samarium iodide (two equivalents) in
Entry No. Ar Ar’ Yield [%]
THF, a rapid reaction due to the fast disappearance of the blue
green colour of samarium iodide gave benzil 63 as shown in
58 a phenyl phenyl 95
Scheme 34.[139] The limited substrate scope reported by the
58 b p-anisyl p-anisyl 97
58 c p-tolyl p-tolyl 95 authors indicated that simple benzil 63 a was formed with the
58 d p-anisyl phenyl 96 78% yield and the acid chlorides containing electron donating
58 e p-chlorophenyl p-chlorophenyl 92
p-OCH3 and electron withdrawing p-chloro substituents gave
58 f p-N,N-dimethylphenyl p-N,N-dimethylphenyl 96
58 g 2-furyl 2-furyl 97 benzils 63 b and 63 c in 69% and 72%, respectively.
58 h o-chlorophenyl o-chlorophenyl 90 Aldehydes can be easily obtained by the reaction of
58 i p-nitrophenyl p-nitrophenyl 92
Grignard reagent or organolithiums with N,N-dimeth-
58 j o,o’-chlorophenyl o,o’-chlorophenyl 85
ylformamide.[140] This reaction can be conveniently modified for
the preparation of benzil derivatives 67 in an excellent yield by
treating tetra-substituted oxamides 64 with organometallic
compounds 65 (Scheme 35).
But this simple protocol is not easily workable as the tetra-
substituted oxamides 64 are not easily formed and even if they
are prepared they do not easily form the benzils 67. However,
this idea has been realized in an effective way by using the
dialkyl oxalates 69 which usually react with secondary amines
Scheme 32. Oxidation of 1,2-diols 55 to benzils 59 using catalytic loading of
TEMPO. 68 only on one ester function to produce the ester amides 69.
In this regard, Mueller-Westerhoff et al.[141] utilized a tailor made
cyclic-diamide viz., 1,4-dimethyl-piperazine-2,3-dione (DMPD)
70. The yield of the reaction with phenyl lithium 71 a was 95%
and with phenylmagnesium bromide 71 b was 84%. Efforts of

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Scheme 33. Synthesis of benzils by the use of oxalylchloride as an acylating agent.
Scheme 34. Diiodosamarium promoted easy coupling of acid chlorides 62
to benzils 63.
getting mixed diketones by reacting simultaneously with
phenyllithium and n-butyllithium yielded more amount of
benzil 72 rather than mixed diketone (Scheme 36).
Acylchromates 73 can be employed effectively as acyl
donors in the Pd-catalyzed acylation of allylic halides. Hence,
unsymmetrical benzil derivatives 75 have been obtained from
iodoarenes 74 and acylchromates 73 in presence of carbon
monoxide using a catalytic amount of Pd(PPh3)4 (Scheme 37).
Acylchromates 73 and iodobenzene 74 were treated under
1 atm CO. A ketone i was also obtained as by product if DCM/
THF was used as a solvent, along with the desired benzil 75. If
Scheme 35. Preparation of benzil 67 from oxamides and Grignard reagent.
Scheme 36. Synthesis of benzils 72 from Phenyllithium/Grignard reagent 71 and DMPD.
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toluene was used, formation of ketone i could be suppressed
and the benzil derivative 75 only was obtained. Excess amount
of iodoarenes 74 were needed in order to obtain the benzil 75
in good yield at room temperature. 75 was synthesized in 74%
yield (1 mol% Pd) or 84% yield (2 mol% Pd) by employing only
iodoarene (1.5 equivalent) when the reaction was performed at
50 °C. A plausible mechanism for the formation of benzil
derivative has been proposed (Scheme 37a).[142]
When an electron donating substituent was introduced on
aryl group of the chromates, the corresponding benzil deriva-
tive 75 was produced in good yield, while introduction of
electron withdrawing group such as CF3 diminished the yield of
75 and the mono-ketone i was also obtained (entries 1–3).
Substituent effect on the iodoarene showed a similar inclination
(entries 4–7, Table 22).
The reaction of acylchromate with arylpalladium iodide
seems to be very facile to form trans-bimetallic complex A. If
aryl (Ar’) migration to CO proceeds fast from the complex B,
which is generated by the ligand exchange from phosphine to
CO, cis-diacyl like complex C might be generated. From the
complex C, reductive elimination proceeds smoothly to give
benzil 75 (Scheme 37a).
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 Review

Scheme 37. Pd-catalyzed cross-coupling reaction for synthesis of unsymmetrical benzil 75. a) Plausible mechanism for the Pd-catalyzed cross-coupling
reaction.

Table 22. Palladium catalyzed preparation of unsymmetrical benzils 75.

encouraged to continue this reaction in presence of the added
Entry No. Ar Ar’ Yield [%]
oxidant viz., FeCl3.6H2O and N,N-dialkyl benzimidazolium salt 77
75 a p-anisyl phenyl 84 (10 mol%). The optimization indicated that N,N-dialkyl benzimi-
75 b p-tolyl phenyl 69
dazolium salts 77 with alkyl group having 8 carbon atoms
75 c p-trifluoromethylphenyl phenyl 59
75 d p-anisyl p-anisyl 83 produced the product 78 with higher yield in water solvent.
75 e p-anisyl p-hydroxyphenyl 70 The effect of substituents on the yields indicated that
75 f p-anisyl p-aminophenyl 71
aromatic aldehydes 76 containing Cl, Br, CH3 gave the
75 g p-anisyl p-acetylphenyl 67
corresponding benzils 78 in higher yields whereas, 3-nitro-
benzaldehyde or 4-nitrobenzaldehyde and 4-hydroxyl benzalde-
hyde were converted into benzils 78 with much lower yields.
N-Heterocyclic carbene (NHCs) 77 are versatile ligands that An improvement in this protocol was carried out by Bi et al.[145]
are used in homogenous transition metal catalysis. A report by They repeated the Iwamoto’s reaction[144] of benzoin condensa-
Jing et al.[143] was the first in which a different method of tion in presence of NHC 77. They observed that if the reaction
formation to benzils 78 from aromatic aldehydes 76 had been mixture was refluxed instead of stirring at room temperature,
reported (Scheme 38). This discovery was serendipitous as the the yield of benzils 78 was found to be increased dramatically
authors extended the benzoin condensation using N,N-dialkyl- to 92% and the reaction was rapid enough and completed in
benzimidazole a known N-heterocyclic carbene as catalyst in 30 minutes. Interestingly, this reaction has been carried out in
water.[144] Jing et al. found that benzils 78 was a by-product in a absence of metal catalyst such as FeCl3.6H2O as against the
small amount (10%) due to oxidation. Hence, they were report by Jing et al.[143] Optimization of the reaction indicated

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Scheme 38. NHC-catalyzed one-pot synthesis of benzils 78 from aldehydes.

the use of NHC with n-octyl group (10 mol%) and refluxing it mechanism for this reaction was traced which indicated the
for 2 hour in presence of aqueous NaOH. The substituent effect initial formation of benzoin which gradually underwent further
was in parallel to the report by Jing et al. (Table 23). oxidation. This indicates that the mechanism involved the two
Zhang et al. developed a procedure for the preparation of steps in one-pot. This was confirmed by the successful
benzils 81 by palladium-catalyzed coupling reaction between conversion of benzil 81 from benzoin under our optimized
arylglyoxals 79, and arylboronic acids 80. The condition of the reaction conditions for 1 h.[146]
reaction was optimized by carrying out a model reaction The substituents on the aromatic rings gave good to
between phenylboronic acid and phenylglyoxal in presence of moderate yields for electron-donating groups. Whereas the
palladium/phosphine systems in air. Benzil was formed as a ortho substituent groups furnished good yields, thus indicating
major product where as a trace amount of benzoin was also ortho substituents have a little influence on this reaction.
formed. Benzil resulted from catalytic oxidation of in situ Unfortunately, with increased hindrance on the aryl groups,
generated benzoin in the presence of palladium in air. The such as mesitylboronic acid, the desired products were not
reactions of different arylboronic acids with various arylglyoxals obtained (Table 24).
were examined to broaden the scope of the reaction. Selenium dioxide mediated oxidation processes have been
As expected, all the reactions with a Pd2(dba)3-trimesityl- recognized in synthetic chemistry, especially for its use in the
phosphine system along with K2CO3 as base in toluene and at presence of acids to promote new C C bond formation. This
65 °C proceeded smoothly to provide the desired products in fact encouraged Myrboh et al.[147] to work on one-pot oxidative
moderate to good yields (Scheme 39). The possible reaction coupling with using selenium dioxide for the synthesis of
benzils from acetophenones 82. The oxidation of aryl methyl
ketones to benzils is well known.[148–149] Myrboh et al. reported
Table 23. Synthesis of NHC-catalyzed benzils 78 by one-pot method. the first one-pot synthesis of benzil 85 and 86 from the
oxidative coupling of aryl methyl ketone 82 and unactivated
Entry No. Ar Jing et al.[141] Bi et al.[143] Yield [%]
Yield [%] arenes 83/84 using SeO2 and p-tolunenesulphonic acid
(Scheme 40).
78 a phenyl 83 85
78 b p-tolyl 75 80 Previously unknown benzils can now be easily prepared by
78 c p-anisyl 70 75 using this method. Interestingly, aryl methyl ketones have been
78 d p-hydroxyphenyl – – easily coupled with polynuclear hydrocarbons, which resulted
78 e p-chlorophenyl 94 94
78 f m-bromophenyl 86 86 in the formation of a new series of unsymmetrical benzils 85/
78 g p-bromophenyl 80 80 86. The generality of the method was further established by the
78 h p-nitrophenyl trace trace reaction between substituted aryl methyl ketones 82, which
78 i m-chlorophenyl 90 90
78 j m-nitrophenyl trace trace contain electron withdrawing or donating groups, with arenes
78 k furan-2-yl <5 85 other than benzene and extended arenes. With both electron

Scheme 39. Synthesis of benzils 81 by palladium-catalyzed coupling reaction.

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Table 24. Palladium-catalyzed coupling reaction for benzils 81. moderate to good yields. The scope of this oxidative coupling
reaction was extended to the reaction of polynuclear hydro-
Entry No. Ar Ar’ Yield [%]
carbons with aryl methyl ketones that bear a wide range of
81 a p-fluorophenyl phenyl 75 substituents. Significantly, naphthalene and anthracene gave
81 b p-chlorophenyl phenyl 70
81 c p-tolyl phenyl 85 better yields of the unsymmetrical benzils when reacted with
81 d p-anisyl phenyl 75 acetophenones that contain electron-withdrawing substituents,
81 e 1-naphthyl phenyl 80 such as chloro, bromo, and nitro groups, on the ring at 35 °C
81 f phenyl phenyl 90
81 g phenyl p-fluorophenyl 67 with acetonitrile as the solvent, compared to benzene and its
81 h phenyl p-chlorophenyl 65 derivatives.
81 i phenyl p-tolyl 90 The mechanism involves the following steps as depicted in
81 j phenyl p-anisyl 75
81 k phenyl 3-thienyl 60 the Scheme 40a. Oxidation of aryl methyl ketones 82 to glyoxal
81 l phenyl 2-thienyl 50 i by SeO2 is followed by the preferential formation of an O Se
81 m phenyl o-chlorophenyl 60 bond through the carbonyl oxygen atom of the aldehyde group
81 n phenyl o-tolyl 80
81 o phenyl 1-naphthyl 80 in presence of para-toluenesulphonic acid, to give the inter-
81 q phenyl p-anisyl 74 mediate ii. The activating effect of the keto group and the
81 r phenyl p-fluorophenyl 75 formation of the O Se bond generated a strong electrophilic
81 s phenyl p-tolyl 85
81 t phenyl p-anisyl 80 centre at the aldehyde carbon atom of ii, which is highly
susceptible to attack from electron-rich arenes to give the
selenite intermediate iii. Oxidative decomposition of iii led to
the final product 85.
withdrawing and donating substituents on the ring, all the Encouraged by these results, the scope of this oxidative
reactions have proceeded to afford unsymmetrical benzils in coupling reaction was extended to the reaction of polynuclear

Scheme 40. Synthesis of unsymmetrical benzils by oxidative coupling. a) Plausible mechanism for the synthesis of one-pot unsymmetrical benzils.

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hydrocarbons with aryl methyl ketones that bear a wide range
Table 25. Synthesis of unsymmetrical benzils by one-pot oxidative cou-
of substituents (Table 25). Significantly, naphthalene and
pling.
anthracene gave better yields of the unsymmetrical benzils 87/
Entry No. Ar in ArCOCH3 Ar’H Yield [%]
88 when reacted with acetophenones that contain electron-
85 a phenyl Benzene 59 withdrawing substituents such as chloro, bromo, and nitro
85 b p-bromophenyl Benzene 58
groups, on the ring at 35 °C with acetonitrile as the solvent,
85 c p-nitrophenyl Benzene 60
85 d p-chlorophenyl Toluene 60 compared to benzene and its derivatives (Table 25).
85 e p-bromophenyl Toluene 61 A para-selective C C coupling reaction to obtain 4-hydrox-
85 f p-nitrophenyl Toluene 62
ybenzil 91 scaffolds from aryl methyl ketones 89 and phenol
85 g m-nitrophenyl o-Xylene 62
85 h m-acetamidophenyl Toluene 67 derivatives 90 has been reported.[150] It is a HI mediated reaction
85 i m-acetamidophenyl Anisole 72 in presence of boric acid at 115 °C for 6 h to obtain directly 4-
86 j 2-napthyl Benzene 59
hydroxy benzils. After the optimization of the reaction con-
86 k 2-napthyl Toluene 51 (isomers)
86 l 2-napthyl p-Xylene 61 ditions, the substrate scope was analyzed and all of them
86 n 2-napthyl Anisole 70 reacted smoothly under this condition (Scheme 41).
87 aa m-anisyl Naphthalene 65
In regard to the scope and tolerance for aryl methyl
87 ab o-hydroxyphenyl Naphthalene 69
87 ac p-hydroxyphenyl Naphthalene 67 ketones, aromatic rings bearing halogen substituents ( F, Cl,
87 ad p-nitrophenyl Naphthalene 70 Br) were all well tolerated in this mild transformation. Nitro
87 ae m-acetamidophenyl Naphthalene 75
groups located at all positions of the aromatic ring also afforded
87 af 2,4-dimethylphenyl Naphthalene 62
87 ag o-tolyl Anthracene 60 the desired products, as expected. Bearing an electron-with-
87 ah p-tolyl Anthracene 57 drawing methylsulfonyl substituent, 91 gave a relatively high
87 ai m-anisyl Anthracene 65
yield. Substitution with sterically bulky substituents showed no
87 aj o-chlorophenyl Anthracene 63
87 ak p-chlorophenyl Anthracene 68 detrimental effects on the yields. This diversity broadens the
87 al p-bromophenyl Anthracene 62 horizon of the reaction’s applicability (Table 26).
87 am o-hydroxyphenyl Anthracene 50
A probable mechanism was depicted in Scheme 41a.
87 an p-hydroxyphenyl Anthracene 57
87 ao m-nitrophenyl Anthracene 64 Initially, HI acted as a reducing agent to react with DMSO and
87 ap p-nitrophenyl Anthracene 66 delivers I2. Acetophenone 89 a underwent iodination to form α-
87 aq m-acetamidophenyl Anthracene 73
iodoketone II, which was smoothly converted to the phenyl-
87 ar 2,4-dimethylphenyl Anthracene 58
87 as 2,4,6-trimethylphenyl Anthracene 53 glyoxal III’ via a Kornblum-type oxidation. Because the hydro-
88 at 2-naphthyl Naphthalene 69 iodic acid reagent was in aqueous solution, water cannot be
88 au 2-furanyl Naphthalene 38
ignored in the reaction system. Compound III’ presumably
88 av 2-thiophenyl Naphthalene 57
88 aw 2-thiophenyl Anthracene 46 transformed into its monohydrate form III, and then its hydrides

Table 26. Substrate scope optimization for the direct synthesis of 4-hydroxybenzils 91.
Entry No. Ar Ar’ Yield [%]

91 a phenyl 4-hydroxy-3-methylphenyl 71
91 b phenyl 4-hydroxy-3,5-dimethylphenyl 76
91 c phenyl 4-hydroxy-3,5-dimethoxyphenyl 73
91 d phenyl 4-hydroxy-3-isopropyl-6-methylphenyl 93
91 e phenyl 4-hydroxy-2-isopropyl-5-methylphenyl 84
91 f phenyl 4-hydroxy-2,6-dimethylphenyl 80
91 g phenyl 4-hydroxy-2,6-dimethoxyphenyl 36
91 h phenyl 4-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl 79
91 i phenyl 4-hydroxynaphthalen-1-yl 75
91 j phenyl 3,4-dihydroxyphenyl 44
91 k phenyl 2-hydroxy-4,5,6-trimethoxyphenyl 82
91 l 4-methoxyphenyl 2-hydroxy-4,5,6-trimethoxyphenyl 77
91 m 4-nitrophenyl 2-hydroxy-4,5,6-trimethoxyphenyl 71
91 n 4-fluorophenyl 4-hydroxy-3,5-dimethylphenyl 80
91 o 4-chlorophenyl 4-hydroxy-3,5-dimethylphenyl 72
91 p 4-bromophenyl 4-hydroxy-3,5-dimethylphenyl 67
91 q 4-nitrophenyl 4-hydroxy-3,5-dimethylphenyl 72
91 r 3-nitrophenyl 4-hydroxy-3,5-dimethylphenyl 51
91 s 2-nitrophenyl 4-hydroxy-3,5-dimethylphenyl 66
91 t 4-(methanesulfonyl)phenyl 4-hydroxy-3,5-dimethylphenyl 78
91 u 4-methoxyphenyl 4-hydroxy-3,5-dimethylphenyl 69
91 v 2-naphthyl 4-hydroxy-3,5-dimethylphenyl 67
91 w 2H-1,3-benzodioxol-5-yl 4-hydroxy-3,5-dimethylphenyl 48
91 x [1,1’-biphenyl]-4-yl) 4-hydroxy-3,5-dimethylphenyl 71
91 y 9H-fluoren-2-yl 4-hydroxy-3,5-dimethylphenyl 76
91 z 1-benzofuran-2-yl 4-hydroxy-3,5-dimethylphenyl 76
91 a’ 1H-indol-3-yl 4-hydroxy-3,5-dimethylphenyl 80
91 b’ 2-furanyl 4-hydroxy-3,5-dimethylphenyl 62

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Scheme 41. Para-selective C C bond coupling between phenols and aryl methyl ketones. a) Probable mechanism for the synthesis of 4-hydroxybenzils.
were abstracted by boric acid to form TS1, incompletely and
with rapid reversibility. This six-membered boric complex ring
activated the phenylglyoxal monohydrate in situ. Meanwhile,
boric acid coordinated with phenolic hydroxyl to prevent the
O H insertion reaction and acted as a steric agent to prevent
ortho-selective attack. The observed para-selective attack led to
the creation of a C C bond in the acid medium, accompanied
by the formation of a five membered boric complex ring (TS2).
Hydrolyzed by water, intermediate IV was furnished. It was then
oxidized by the terminal oxidant I2, which was provided by the
combination of HI with DMSO. As another product, HI was
released to close the catalytic cycle. The desired product 4-
hydroxybenzil derivatives 171 could be obtained after workup.
As a testament to the utility of this method, target-oriented
compounds were specified. The pharmaceutical candidate NSC
115566 93[151] which is considered difficult to synthesize, can be
obtained from the reaction between simple acetophenone 92
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Review
and phenol under our conditions, followed by an alkylation
reaction, in 47% overall yield (Scheme 42). Moreover, this
coupling reaction has definite potential to open up new vistas
in the total synthesis of 4-hydroxybenzil natural products.
A highly efficient, one-pot, oxidative coupling of aryl methyl
ketones 94 with anilines 95 to p-amino-substituted benzils 96
and their iodo derivatives 97 was reported.[152] It is interesting to
note that the amino group remains unaltered without any
chemical change in this reaction with a scope to utilize further.
After optimization using various mole percent of iodine,
additives such as CuO, TBHP, DTBP, Oxone, MnO2, CuBr2, CuCl2,
Cu(OAc)2, CuI, the optimization was observed to be aniline 95
(1.6 equiv) to acetophenone 94 in presence of iodine (1 equiv)
with CuO (1 equiv) as the additive and a reaction temperature
of 100 °C. However, iodination at ortho to amino group 97 was
observed when two equivalents of iodine were used
(Scheme 43). The reaction was found to be applicable to a wide
© 2021 Wiley-VCH GmbH

Scheme 42. Preparation of pharmaceutical candidate NSC 115566.
Scheme 43. One-pot synthesis of p-amino-substituted unsymmetrical benzils 96. a) Experimental insights for the plausible mechanism.
range of aromatic ketone substrates and aromatic anilines and
the substrate scope has been enlisted in the Table 27.
Based on the control experiments and optimisations, a
plausible mechanism was proposed in Scheme 43a. Initially,
acetophenone 94 was converted into intermediate A in the
presence of I2/CuO and DMSO by a Kornblum oxidation. CuO
and DMSO could convert in situ generated HI into iodine and
realize a catalytic cycle for regeneration of the iodine. Then a
Friedel-Craft’s type reaction between intermediate A and aniline
affords compound B which could be further converted to benzil
96 through intermediate C in the presence of iodine. Although
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the conversion of C to 96 with imine D as the intermediate had
been confirmed, the direct oxidation of B to 96 cannot be ruled
out. When the amount of iodine was in excess, 96 was further
transformed into the iodo-product 97 (Scheme 43a).
An operationally simple one-pot, two-step procedure for
the desymmetrization of benzils was reported by Massi and
Bortolini.[153] This consists of the chemoselective cross-benzoin
reaction of symmetrical benzils 98 with aromatic aldehydes 99
catalyzed by the methyl sulfinyl (dimsyl) anion, followed by
microwave-assisted oxidation of the resulting benzoylated
benzoins with nitrate, which concurrently avoids the costly
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 Review

Table 27. Substrate scope for synthesis of p-amino-substituted unsymmetrical benzils 96.
Entry No. Ar in ArCOCH3 Aromatic aniline Yield [%] Yield [%]
176 177

96 a/97 a phenyl p-aminophenyl 59 53

96 b/97 b p-chlorophenyl p-aminophenyl 61 56
96 c/97 c m-chlorophenyl p-aminophenyl 57 48
96 d/97 d o-chlorophenyl p-aminophenyl 56 52
96 e/97 e p-bromophenyl p-aminophenyl 62 62
96 f/97 f p-nitrophenyl p-aminophenyl 52 53
96 g/97 g p-anisyl p-aminophenyl 41 37
96 h/97 h o-tolyl p-aminophenyl 53 –
96 i/97 i m-tolyl p-aminophenyl 56 –
96 j/97 j p-tolyl p-aminophenyl 58 60
96 k/97 k p-terbutylphenyl p-aminophenyl 54 –
96 l/97 l 2-naphthyl p-aminophenyl 60 61
96 m/97 m 1-naphthyl p-aminophenyl 63 58
96 n/97 n 3-pyridyl p-aminophenyl 46 43
96 o/97 o 4-pyridyl p-aminophenyl 51 –
96 p/97 p 2-furanyl p-aminophenyl 33 –
96 q/97 q Benzo[b]furan-3-yl p-aminophenyl 43 –
96 r/97 r phenyl 4-amino-3-methyl 55 –
96 s/97 s phenyl 4-amino-2-methyl 53 –
96 t/97 t phenyl 4-amino-2-methoxy 51 –
96 u/97 u phenyl 4-amino-3-chloro 29 –

isolation procedure. Both electron-withdrawing and electron-
donating substituents on the aromatic rings were investigated
for the synthesis of unsymmetrical benzil. This method
employed commercial or readily available starting materials,
avoid the use of toxic reagents, and can be easily adaptable to
the preparation of a diversified library of benzils 100
(Scheme 44). The classical aldehydes behave as umpolung of
electrophiles alternatively.
The proposed mechanism, showed that by direct deproto-
nation of DMSO with a base the methylsulfinyl (dimsyl) anion A
was obtained, which was an effective replacement of hazardous
cyanide sources for the polarity reversal of symmetrical benzils
98 in cross-benzoin condensations with aldehydes 99 (Sche-
me 44a). The reference of the dimsyl anion for α-diketone over
aldehyde addition, and the aptitude of the generated acyl anion
equivalent C to intercept the aldehyde 99 (cross-coupling)
rather than a second molecule of 98 (homo-coupling). By this
strategy, the benzoylated benzoin product i was obtained with
a high efficiency in a fully atom-economic manner. It is
noteworthy that the dimsyl anion belongs to the restricted class
of organocatalysts capable of promoting umpolung trans-
formations. Overall, the sequence was none other than the
desymmetrization of a symmetrical benzil 98, with the advant-
age that the aryl substituents of the final benzil 100 may be
chosen independently (Scheme 44a). The scope of the oxidation
step was explored with the optimal conditions identified and
exploring different symmetrical benzils 98 and aromatic
aldehydes 99 (Table 28).
Kim et al. reported the expedient synthetic route of benzil
derivatives 103 from aryl bromides and vinylene carbonate a
glyoxal equivalent in a palladium-catalyzed reaction.[154] The
reaction sequence involved Heck-type diarylation reaction with
aryl bromides 101 and vinylene carbonate to form 4,5-diaryl-
1,3-dioxol-2-one, ring-opening to benzoin derivative, and an

Table 28. Substrate scope for the desymmetrization of symmetrical benzils 98.
Entry No. Ar Ar’ Yield [%] Yield [%] Yield [%]
i ii 100

1 phenyl o-chlorophenyl 95 0 85, 78

2 phenyl o-bromophenyl 87 0 74, 65
3 phenyl p-chlorophenyl 76 19 84, 76
4 phenyl p-bromophenyl 46 27 79, 61
5 phenyl m-bromophenyl 88 5 85, 71
6 phenyl 1-naphthyl 58 0 73, 40
7 phenyl o-tolyl 90 0 85, 73
8 phenyl o-anisyl 71 0 70, 45
9 p-bromophenyl m-bromophenyl 86 5 87, 73
10 p-bromophenyl o-tolyl 71 0 61, 36
11 p-tolyl m-bromophenyl 86 5 75, 62
12 p-tolyl o-tolyl 52 0 73, 5
13 phenyl o-trifluoromethylphenyl 78 0 82, 60
14 p-trifluoromethylphenyl o-bromophenyl 79 0 77, 51
15 phenyl 2-furyl 8 84 17, 11
16 2-pyridyl o-chlorophenyl 95 0 25, 21

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Scheme 44. One-pot, desymmetrization of symmetrical benzils catalyzed by the methylsulfinyl (dimsyl) anion. a) Plausible mechanism for the cross-coupling
of symmetrical benzils 98 with aromatic aldehydes 99 mediated by the dimsyl anion A and the designed two-step sequence towards unsymmetrical benzils
100.
oxidation process to furnish benzil derivatives 103 depicted in
Scheme 45.
The formation of benzils 103 was postulated by the
mechanism as shown in Scheme 45a. Syn-carbopalladation of
ArPdBr to vinylene carbonate produced an intermediate I,
which has no syn-β-hydrogen atom with respect to PdBr
moiety. Rather, compound 102 was formed via a facile
deprotonation of the oxonium ion intermediate II produced via
an SN1 type solvolysis process. It was noted that the subsequent
arylation of 102 produced III by the same mechanism. Ring-
opening of compound III produced benzoin IV presumably by
moisture in the basic reaction mixture. The oxidation of IV to
103 was found in two parts, (i) by a base-mediated aerobic
oxidation & (ii) a Pd0/101 mediated redox process which
converted IV to 103 and also 101 to biphenyl V at the same
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time. The studies involving reaction conditions from the very
outset used K2CO3 in DMF at 90 °C however; benzil 103 was
produced in low yields. The yields were increased by use of
Cs2CO3 in CH3CN, and further under DMF/Cs2CO3. Finally,
10 mol% of a palladium catalyst improved the yield of benzil
103 to 81% at 120 °C within 30 min as given in Table 29.
5. Miscellaneous Methods
This section discusses the methods which do not fall under any
of the above sections. Benzil 1 is a standard building block in
organic synthesis which condenses with amines to give
diketimine ligands. It can be nitrated in excess cold fuming
nitric acid, sulphuric acid in presence of KNO3 to form three
© 2021 Wiley-VCH GmbH
 Review

Scheme 45. Palladium-catalyzed synthesis of benzils 103 from aryl bromides. a) Plausible mechanism for the formation of substituted benzils 103.

Table 29. Substrate scope for the expedient synthesis of benzils 103. corresponding benzils 105 into excellent yields (Scheme 46).
Entry No. Ar Yield [%] The prominent yields of benzils 105 were obtained when the
103 a phenyl 81 reaction conditions were optimized when deoxybenzoins was
103 b p-tolyl 78 treated with N,N-dimethylformamide in the presence of
103 c o-tolyl 74 20 mol% of DABCO loading at 90 °C in air.
103 d p-anisyl 59
103 e m-anisyl 71 The formation of benzils was formulated by the plausible
103 f p-chlorophenyl 59 mechanism (Scheme 46a) by the deprotonation of the deoxy-
103 g 1’-naphthyl 76 benzoin 104 to carbanion I by DABCO, which then reacts with
103 h 2’-naphthyl 67
103 i m-acetylphenyl 55 triplet oxygen by a radical chain process to afford the α-
103 j p-acetylphenyl 41 hydroperoxyketone anion II. This further gives intermediate III
that undergoes elimination process in presence of DABCO to
benzil product 105. It was noted that all the deoxybenzoin 104
reactions with electron-withdrawing substituents investigated
dinitrobenzils viz., m,m’-dinitro, o,m’-dinitro and o,o’-dintro underwent the oxidation smoothly to give the corresponding
benzil derivatives in about 70, 20 and 10% yield respectively.[155] benzils 105 in excellent yields (Table 30).
Benzil is stereo-specifically reduced to (S)-benzoin by enzyme Goggiamani et al.[158] also reported efficient and novel
“Benzil reductase IRC24”.[156] copper-catalyzed synthesis of benzils 106 from deoxybenzoins
After investigating the importance of the benzils and their 104 under neutral conditions using air as the oxidant has been
types of formations from organic substrates, deoxybenzoins developed. The reaction proceeded with optimized conditions
were also scrutinized for the benzil preparations. In view of this, involving Cu(OAc)2 (15 mmol%), triphenyl phosphine
Jiang and co-workers[157] reported an 1,4-diazabicyclo[2.2.2] (30 mmol%) in aerobic conditions at satisfactory yields given in
octane (DABCO) catalyzed aerobic oxidation of deoxybenzoins Scheme 47. It was proposed by the authors that formation of
104 involving air as the sole oxidant efficiently to give the benzils (Scheme 47a) was by preliminary formation of the

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Scheme 46. Synthesis of benzils by DABCO-catalyzed aerobic oxidation of deoxybenzoin. a) Plausible mechanism for the aerobic-oxidation of benzils 105.

Table 30. Aerobic oxidation of deoxybenzoins 104 catalyzed by DABCO in

DMF. derivative 106. The copper(I) catalyst was reoxidized to the
Entry No. Ar Ar’ Yield [%] active copper(II) catalyst by oxygen.
From the optimized conditions, it was developed that the
105 a phenyl phenyl 95
105 b phenyl p-bromophenyl 99 protocol affords benzils 106 from deoxybenzoins 104 in
105 c phenyl p-chlorophenyl 100 moderate to excellent yields and the method was well-tolerated
105 d p-chlorophenyl phenyl 93
by a variety of substituents depicted in Table 31.
105 e m-chlorophenyl phenyl 99
105 f o-chlorophenyl phenyl 95 For the successful transformation of deoxybenzoins to
105 g p-tolyl phenyl 98 benzils, a mild, general and efficient method using copper(II)-
105 h p-anisyl phenyl 97
catalyzed base-accelerated oxidation of C H Bond to synthesize
105 i p-anisyl p-anisyl 100
105 j naphthyl phenyl 95 benzils 107 was reported by Wang and co-workers[159] in 2015.
105 k p-anisyl methyl 46 To achieve highest yields of benzils 107, the reaction was
105 l p-fluorophenyl methyl 0
optimized by treating deoxybenzoins 104 with Cu(OAc)2.H2O
105 m ethyl phenyl 0
(5 mol%), K2CO3 (5 mol%) using molecular oxygen as terminal
oxidant at low temperatures (Scheme 48). For the plausible
mechanism (Scheme 48a), the deoxybenzoin 104 undergoes
benzylic radical I from deoxybenzoin 104 by the reduction of oxidation with Cu (II) and deprotonation to obtain benzyl
the copper (II) catalyst to copper (I). The reaction of 104 with radical I. The benzyl radical was trapped by oxygen to produce
oxygen gave the peroxoradical II which was later transformed the peroxide radical II, followed by capture of a hydrogen
into the hydroperoxide III via the capture of a hydrogen radical radical to III and the elimination of H2O to produce correspond-
with the elimination of water molecule to afford benzil ing benzils 107.

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Scheme 47. Copper-catalyzed oxidation of deoxybenzoins 104 to benzils 106. a) Reaction mechanism for aerobic Cu-catalyzed oxidation of deoxybenzoin.

Table 31. Copper-catalyzed aerobic oxidation of deoxybenzoins 104.

In the same year, Ravikumar et al.[160] reported the new
Entry No. Ar Ar’ Yield [%]
conceptual method viz., dimethyl sulfoxide (DMSO) based
106 a phenyl phenyl 95 oxidation for the synthesis of benzils. Two comparatively
106 b p-anisyl phenyl 55
106 c p-chlorophenyl p-iodophenyl 70 methods were developed for the oxidation of the active
106 d phenyl p-cyanophenyl 66 methylene group in the deoxybenzoin 104 to benzils 108 with
106 e phenyl p-anisyl 62 significant yields. The reaction method undergoes oxidation
106 f phenyl p-tolyl 70
106 g phenyl o-tolyl 45 very smoothly to afford benzils 108 in higher yields ranging
106 h phenyl p-carbmethoxyphenyl 72 (86-97%) in shorter reaction time summarized in (Scheme 49)
106 i p-chlorophenyl phenyl 53 and Table 33.
106 j phenyl p-iodophenyl 60
106 k phenyl p-bromophenyl 75 In the recent decades, considerable work was carried out in
106 l p-chlorophenyl p-bromophenyl 60 oxidative rearrangements for the synthesis of benzils 1.
106 m p-chlorophenyl p-anisyl 56 Amongst them, α,β-unsaturated diaryl ketones or chalcones
106 n p-anisyl p-anisyl 51
106 o o-bromophenyl phenyl 62 109 was one of the substrates investigated in the early 1970s
by McKillop[161] & Taylor[162] for the synthesis of benzils 110.
Thallium(III) nitrate (TTN) was used as an oxidant in perchloric
acid medium (Scheme 50). Whereas, both the methods utilize
Various deoxybenzoins 104 possessing either electron-with- highly toxic thallium salt (TTN) as strong oxidant in harsh acidic
drawing groups or electron-donating groups on both aromatic conditions yielding in a moderate range of benzils 110.
rings provided benzils 107 in good to excellent yields in the For the improved yields of benzils, mild reactions con-
ranges 73–92% (Table 32). It was noted that the substrates ditions, simple work-up procedure, new methods were devel-
containing electron-withdrawing groups on either side of oped as reported by Li and co-workers.[163] The reaction
phenyl ring reacts faster than those substituted by electron- proceeded via copper-mediated aerobic oxidative cleavage of
donating groups. α,β-unsaturated ketones 109 to furnish corresponding benzils

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Scheme 48. Cu(II)-catalyzed base-accelerated oxidation of benzils 107 from deoxybenzoins. a) Proposed mechanism for Cu(II)-catalyzed oxidation of
deoxybenzoins 104.

Table 32. Cu(II)-catalyzed base-accelerated oxidation of benzils 107.

111 using potassium acetate as a catalyst and sodium iodide as
Entry No. Ar Ar’ Yield [%] a promoter (Scheme 51).
107 a phenyl phenyl 91 The formation of these various benzils were postulated by
107 b p-tolyl phenyl 76 the plausible mechanism depicted in Scheme 51a by the
107 c phenyl p-tolyl 83
107 d p-anisyl phenyl 65 formation of epoxide A starting from α,β-unsaturated ketones
107 e phenyl p-anisyl 90 under air, initially. The intermediate A was further attacked by
107 f p-nitrophenyl phenyl 82 I in presence of acetic acid to furnish C & D via the formation
107 g p-fluorophenyl phenyl 92
107 h phenyl p-fluorophenyl 84 of B. On treatment with water molecule, the iodide ion was
107 i p-chlorophenyl phenyl 90 replaced by the hydroxyl group to α-hydroxy dicarbonyl
107 j phenyl p-chlorophenyl 87 compound E followed by a further oxidation to tricarbonyl
107 k o-bromophenyl phenyl 76
107 l m-bromophenyl phenyl 90 compound F under air. It undergoes 1,2-Wagner-Meerwein-type
107 m p-bromophenyl phenyl 92 rearrangement of carbonyl group of F to give H via the Cu(II)
107 n phenyl p-bromophenyl 92 complex G. Finally, the product benzils 111 were formed by the
107 o p-bromophenyl p-fluorophenyl 91
107 p p-bromophenyl p-anisyl 73 elimination of carbon monoxide and Cu(II) from intermediate H.
107 q p-tolyl p-fluorophenyl 87 It was investigated looking into the optimized conditions,
107 r p-tolyl p-anisyl 86 that α,β-unsaturated ketones 109 bearing both electron-
107 s p-tolyl p-tolyl 73
107 t phenyl 2-methylthiophenyl 86 donating ( CH3, OCH3) and electron-withdrawing ( Cl, F,
NO2) groups on phenyl rings could easily tolerate the reaction
conditions (Table 34). From the substrate scope, it was noted

Scheme 49. The DMSO based oxidation of deoxybenzoin 104 to benzil 108.

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that electron-donating substituents afforded desired benzils
111 in slightly higher yields than electron-withdrawing sub-
stituents.
On the other hand, Suryavanshi et al.[164] reported a metal-
free oxidative rearrangement of α,β-unsaturated diaryl ketones
Table 33. Substrate scope and reaction yields of DMSO-based oxidation of
deoxybenzoin. 109 using I2/TBHP for the synthesis of benzils 112 in good to
high yields (Scheme 52). These scaffolds were built as they
Entry No. Ar Ar’ Yield [%]
served as a synthon to many medicinally important molecules.
108 a p-anisyl phenyl 96 The method was smoothly conducted for various substrates
108 b 3,4-dimethoxyphenyl phenyl 90
108 c 1,3-benzodioxyl phenyl 95 such as electron-donating as well as electron-withdrawing
108 d o-chlorophenyl phenyl 86 group giving higher yields of former when compared to the
108 e p-chlorophenyl phenyl 91 later substituents.
108 f 3-thiophenyl phenyl 85
108 g phenyl phenyl 96
The transformation proceeds via oxidative aryl migration,
108 h phenyl p-fluorophenyl 96 followed by C C bond cleavage illustrated in mechanism

Scheme 50. Oxidative rearrangement of chalcones 109 to benzils 110.

Scheme 51. Aerobic oxidative cleavage of α,β-unsaturated ketones 109 to benzils 111. a) Plausible mechanism for the Cu(II)-catalysed formation of benzils
111.

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Table 34. Substrate scope & reaction yields by copper-mediated synthesis Table 35. Substrate scope and isolated yields for the formation of benzils
of benzils 111. 114.
Entry No. Ar Ar’ Yield [%] Entry No. Ar Ar’ Yield [%]

111 a phenyl phenyl 83 114 a phenyl phenyl 92

111 b p-tolyl p-tolyl 78 114 b p-bromophenyl phenyl 94
111 c phenyl p-anisyl 86 114 c p-chlorophenyl phenyl 95
111 d phenyl p-tolyl 71 114 d p-tolyl phenyl 80
111 e 1,3-benzodioxyl phenyl 88 114 e 2,5-dimethylphenyl phenyl 75
111 f 1,3-benzodioxyl p-tolyl 82 114 f p-anisyl phenyl 85
111 g p-fluorophenyl p-anisyl 75 114 g p-chlorophenyl p-fluorophenyl 77
111 h p-fluorophenyl phenyl 72 114 h p-anisyl p-fluorophenyl 61
111 i p-chlorophenyl p-anisyl 68 114 i p-tolyl p-fluorophenyl 83
111 j o-chlorophenyl p-anisyl 75 114 j p-bromophenyl p-fluorophenyl 76
111 k o-chlorophenyl p-tolyl 73 114 k 2,5-dimethylphenyl p-fluorophenyl 75
111 l p-chlorophenyl p-tolyl 82 114 l p-isopropyl phenyl p-fluorophenyl 68
111 m o-chlorophenyl p-chlorophenyl 70 114 m p-anisyl p-anisyl 27
111 n 2,4-dichlorophenyl p-chlorophenyl 66 114 n naphthyl phenyl 63
111 o phenyl p-chlorophenyl 73
111 p p-nitrophenyl phenyl 61

Benzil derivative viz., 4,4’-dibromobenzil 119 has been

Scheme 52a. The reaction proceeds with the preliminary synthesized by reacting benzoin 9 with urea in halohydrocar-
initiation of tertiary butyl peroxide radical from 2 moles of bon as solvent to form 4,5-diphenylimidazol-2-one 117. This
tertiary butyl hydrogen peroxide, undergoing 1,4-addition was further brominated to 4,5-bis-(4-bromophenyl)-imidazol-2-
across α,β-unsaturated ketones 109 in presence of I2, giving an one 118 which upon oxidation in nitric acid gave 119
intermediate A. Intermediate A in presence of DMSO gets (Scheme 55).[167]
oxidized to intermediate B by Kornblum oxidation with the An efficient oxidation of α-haloketones 120 to the corre-
elimination of dimethyl sulfide. The homolytic cleavage of the sponding benzil derivatives 121 at room temperature has been
intermediate B of the tertiary butyl peroxide part leads to C. reported by Su and co-workers.[168] Natural sunlight and air were
Lastly, a radical rearrangement of C gives benzil product 112 successfully utilized in this approach through the combination
giving out formyl radical. of photocatalysis and organocatalysis viz., the use of Ru(bpy)3Cl2
The exclusive oxidative rearrangement on α,β-unsaturated (0.50 mol%) as catalyst in presence of 4-methoxypyridine and
ketones was extended with enaminone substrates to achieve organic base such as lithium carbonate as shown in Scheme 56
corresponding benzils at higher yields. Wan and co-workers[165] (Table 36).
investigated the efficient formation of benzils 114 under Hayashi et al.[169] reported the benzil derivatives by nitroxyl-
ambient conditions through visible-light catalysis in the pres- radical-catalyzed oxidation of silyl enol ethers using magnesium
ence of Rose Bengal (Scheme 53). It is metal-free photocatalytic monoperoxyphthalatehexahydrate (MMPP.6H2O) as the co-
C=C double bond cleavage of enaminones 113 at room oxidant.
temperature, which was well-studied for various substituents on Hunter and Barton reported a method for benzils using
the aromatic ring to achieve good to excellent yields of benzils oxoammonium ion derived from 2,2,6,6-tetramethylpipedine-1-
114. oxyl (TEMPO) 122 (Figure 5).[170] They observed that α-aminooxy
Rose Bengal based photocatalysis was elaborated by ketones formed due to addition of ketones to oxoammonium
proposed mechanism shown in Scheme 53a. The photo-
induction of Rose Bengal (RB) provides the excited state of RB
as RB* which in turn returns to the ground state of RB by Table 36. Utilization of sunlight and air for the synthesis of benzil
compounds.
producing the production of singlet oxygen. The singlet oxygen
then attacks the enaminones 113 to give peroxide intermediate Entry No. Ar Ar’ X Yield [%]
i which decomposes to provide the benzil derivatives 114. 121 a phenyl phenyl Cl 81
After the satisfactory optimization of the reaction methods, 121 b phenyl phenyl Br 81
121 c p-anisyl p-anisyl Cl 60
it was observed that the effect of substituents on the aromatic
121 d p-anisyl p-anisyl Br 72
rings of enaminones 113 was not observed and probabilities of 121 e phenyl p-chlorophenyl Cl 82
the formation of corresponding benzils 114 were in good to
excellent yields (Table 35). The method conveniently tolerated
variety of functional groups; including alkyl, alkoxyl, and
halogen in both the aromatic rings to furnish benzil derivatives
114.
Synthesis of various benzils 116 containing a substituent on
only one phenyl ring or two different substituents on both the
phenyl rings respectively, through epoxy chalcone 115 has
been described (Scheme 54).[166] Figure 5. Nitroxyl-radical appended reagents for oxidation.

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Scheme 52. Oxidative rearrangement for benzils 112 using I2/TBHP. a) Transformation of α,β-unsaturated diaryl ketones 109 to benzils 112.
ion were converted into benzils by thermolysis. This method
required the stoichiometric amount of TEMPO 122 for the
formation of benzils and hence rarely used. To address this
issue Hayashi et al. developed a redox catalytic cycle, in which
the oxidation of α-aminooxy ketone intermediate to N-oxide
regenerates oxoammonium ions thereby completing the cata-
lytic cycle. They envisaged that a less hindered class of nitroxyl
radicals, such as AZADO (2-azaadamantane N-oxyl) 123 and
Nor-AZADO (9-azanoradamantane N-oxyl) 124 (Figure 5) will
accommodate productive interactions between an intermediate
and an oxidant (Scheme 57).
The substrate silyl enol ether 125 was treated with the
AZADO 126 with which the addition proceeded rapidly and the
alkoxyl amine 127 was formed quantitatively. Further, the clean
oxidation to benzil derivative 128 was realized by one-pot
oxidation of 207 in presence of MMPP.6H2O as the oxidant.
Asian J. Org. Chem. 2022, 11, e202100650 (39 of 46)
Review
Hindered TEMPO did not work as a catalyst under the
conditions. The authors also attempted the reaction of deoxy-
benzoin instead of silyl enol ether 125 under the optimized
catalytic conditions (Table 37, entry 6), in which no 128 was
formed. The scope and limitations of this catalytic system as
shown in Table 37 indicated that an electron-withdrawing
group at the aromatic ring lowered the yield (55%, Table 37,
entry 5). Interestingly, the heterocyclic substrates such as indole
and benzoxazole derivatives were converted into their corre-
sponding benzils in high yields (81–89%, Table 37, entries 10
and 11).
A plausible pathway for the catalytic oxidation of silyl enol
ethers to benzils was outlined in Scheme 57a. The reaction
involves the initial formation of the α-aminooxy ketone i with
the addition of 125 to Nor-AZADO + X , which was generated
in situ through the oxidation of Nor-AZADO. Then, 128 and Nor-
© 2021 Wiley-VCH GmbH
 Review

Scheme 53. Metal-free photocatalytic benzil 114 synthesis from enaminones 113. a) Proposed mechanism for Rose Bengal based photocatalysis of
enaminones 113.

Scheme 54. Synthesis of benzil derivatives 116 from epoxy chalcones.

Table 37. Limitation & scope for the catalytic oxidation of silyl enol ether Yang and co-workers developed and reported the synthesis
to benzils 128.
of unsymmetric benzils 130 from β-ketoaldehydes 129 which
Entry Ar Ar’ Yield
provides a very convenient and straightforward protocol.[171]
No. [%]
Under mild reaction conditions, better yields of unsymmetric
128 a phenyl phenyl 86 benzils 130 bearing functional groups were obtained wherein,
128 b phenyl p-tolyl 85
128 c p-chlorophenyl phenyl 81 α,α-dichloroketone was the key intermediate. The method
128 d p-bromophenyl phenyl 81 follows sequence in propagation by generation of α,α-dichlor-
128 e p-fluorophenyl phenyl 83 oketones from β-ketoaldehydes 129, including oxidation by
128 f p-cyanophenyl phenyl 55
128 g p-anisyl p-anisyl 84 sodium hypochlorite, decarboxylation, and chlorination by Cl2
128 h p-chlorophenyl p-chlorophenyl 68 generated from sodium hypochlorite (Scheme 58).
128 i m-chlorophenyl phenyl 76 Considering the optimum conditions in account, the
128 j o-chlorophenyl phenyl 63
128 k 1-(benzenesulfonyl)-1H-indol-2-yl p-anisyl 89 substrate scope was determined as represented in Table 38. No
128 l benzofuran-2-yl p-anisyl 81 significant difference was observed in reactivities between 3-
128 m phenyl iso-propyl 68 oxo-2,3-diphenylpropanal and its derivatives containing elec-
tron-donating groups or electron-withdrawing groups. It was
also found that the reaction was not sensitive to steric
AZADOH were produced through the oxidation of i by hindrance. The heterocyclic groups also afforded corresponding
MMPP.6H2O. Nor-AZADOH was oxidized to Nor-AZADO + X by heteroaromatic products in excellent yields.
MMPP.6H2O to complete the catalytic cycle.

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 Review

Scheme 55. Synthesis of 4,4’-dibromobenzil 119 from benzoin and urea.

acids (I), and then decarboxylation of I provided deoxybenzoins

(III); chlorination of III by chlorine, released from the decom-
position of NaClO in water produced α,α-dichloroketones (V)
which were hydrolyzed in the presence of acetic acid and finally
afforded the desired benzils 130 (Scheme 58a).
Interestingly, Villemin et al.[172] also carried out oxidation of
Scheme 56. Synthesis of benzil 121 from aerobic oxidation of α-haloke- 1,2-dibromides 131 efficiently to get the benzil derivatives 132
tones. under conventional as well as microwave irradiation using
dimethyl sulphoxide. The reaction was expected to involve
bisalkoxy sulfonium salt which underwent elimination of dimeth-
Table 38. Substrate scope and isolated yields for conversion of β- yl sulphide from the adjacent carbon atoms to yield the benzil
ketoaldehydes 129.
derivatives 132 (Scheme 59).
Entry No. Ar Ar’ Yield [%]
Evidently, among various hypervalent iodine reagents, 2-
130 a phenyl phenyl 84 iodoxybenzoic acid (IBX) was found to be a versatile oxidizing
130 b o-tolyl phenyl 90 agent because of its high efficiency, easy availability, mild
130 c o-anisyl phenyl 93
130 d p-anisyl phenyl 85 reaction conditions, and its stability to moisture and air. The
130 e p-anisyl p-anisyl 87 direct conversion of 1,3-diols 133 to benzils 134 by oxidative
130 f p-bromophenyl phenyl 86 cleavage of the C C bond using 2-iodoxybenzoic acid (IBX) in
130 g o-anisyl o-bromophenyl 93
130 h o-anisyl m-bromophenyl 91 dimethyl sulfoxide at ambient temperature (Scheme 60) has
130 i o-anisyl p-bromophenyl 92 been reported.[173] 1,3-diynes delivered substituted benzils in
130 j o-anisyl p-iodophenyl 94 moderate yields via metal-free approach using tetra-n-butylam-
130 k o-anisyl m-chlorophenyl 86
130 l o-anisyl p-anisyl 89 monium iodide (TBAI) as a catalyst and peroxide as a radical
130 m o-anisyl m-anisyl 87 initiator and oxidant.[174]
130 n o-anisyl p-tolyl 91
130 o o-anisyl p-trifluoromethylphenyl 92
130 p o-anisyl furyl 92
130 q o-anisyl thiophenyl 92 6. Conclusions & Future Perspectives

In this review, we have attempted to summarize and classify

A pathway was proposed for the aqueous sodium hypo-
chlorite-mediated transformation of β-ketoaldehydes 129 to
benzils 130. Oxidation of β-ketoaldehydes 129 by sodium
hypochlorite gave the corresponding 3-oxo-2,3-diarylpropanoic
the methods of synthesis of benzils with variety of reagents or
reaction conditions from the year 1836–2021. From the past
centuries, the chemistry of benzils and synthetic methods of
benzils have evolved for its advancement and applications in
various perspectives of survival. The present review includes

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 Review

Scheme 57. Catalytic oxidation using oxoammonium ion stoichiometrically. a) Plausible reaction pathway for synthesis of 1,2-diketones.

Scheme 58. Synthesis of β-ketoaldehydes to benzils 130 using NaClO as an oxidant. a) Possible reaction pathway for preparation of unsymmetrical benzils
130.

both quantitative ie., meta-analytic and also is a narration of derivatives. This provides a conceptual frame work & gives all
qualitative component in the synthesis of benzil and its the synthetic chemists who are working in the medicinal as well

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 Review
7. Abbreviations

AZADO 2-azaadamantane N-oxyl

BTI/PIFA [Bis(trifluoroacetoxy)iodo]benzene
CA-4 Combretastatin A-4
CAN Cerium(IV) ammonium nitrate
DABCO 1,4-diazabicyclo[2.2.2] octane
Scheme 59. DMSO catalyzed oxidation of 1,2-dibromides to benzil 132. DCM Dichloromethane
DMAP 4-dimethylamino pyridine
DMF N,N-dimethylformamide
DMPD 1,4-dimethyl-piperazine-2,3-dione
DMS Dimethyl sulfide
DMSO Dimethyl sulfoxide
DTBP Di-tert-butyl peroxide
GO Graphene oxide
HBr Hydrobromic Acid
Scheme 60. Conversion of 1,3-diols 133 into benzils 134 by IBX. HFIP Hexafluoroisopropanol
IBX 2-Iodoxybenzoic Acid
LED Light Emitting Diode
as material chemistry a state-of-the-art snapshot of synthetic MEC-31 N,N-difluoro-2,2’-
methods to benzil and its analogs. The chemists can make use bipyridiniumbis(tetrafluoroborate)
of this review to follow an appropriate protocol to obtain the MMPP.6H2O Monoperoxyphthalatehexahydrate
benzil by comparing different methodologies enumerated. The MTO Methylrhenium trioxide
synthetic methods for oxidation involved metal-catalyzed, NBS N-bromosuccinimide
inorganic reagents based, air oxidation, photochemical oxida- NCS N-chlorosuccinimide
tion or the use of precursors which are more favourable for NGP Neighbouring group participation
oxidation to furnish benzils easily. Depending on the classifica- NHCs N-Heterocyclic carbenes
tions it was found that from precursors listed above diary- NIS N-iodosuccinimide
lalkynes (tolanes) were explored the most. Amongst various Nor-AZADO 9-azanoradamantane N-oxyl
reagents sole hypervalent iodine, DMSO or combination of I2/ Oxone Potassium Peroxymonosulfate
DMSO was used frequently as an oxidant. PCM Polarisable continuum model
Environmental benign conditions were also enlisted for a PTSA p-tolunenesulphonic acid
mild, clean and greener method for benzils. These reactions are QFC Quinolinium fluorochromate
diverse in nature and have been employed for syntheses in RB Rose Bengal
particular, a wide variety of heterocyclic systems spanning from SAR Structure activity relationship
5-membered ring systems to macro heterocycles. In the carbon- S-L coupling Sonogashira-Linstrumelle coupling
carbon bond forming reactions, palladium-catalyzed coupling TBAI Tetra-n-butylammonium iodide
reactions were investigated whereas the miscellaneous meth- TBAPI Tetrabutylammonium periodate
ods involved transformations from deoxybenzoin, α,β-unsatu- TBHP tert-butyl hydroperoxide
rated diaryl ketones, enaminones, epoxychalcones, α-haloke- TBN Tert-butyl nitrite
tones, α-aminoketones, β-ketoaldehydes, 1,3-diynes, 1,3-diols & TCM Trichloromelamine
1,2-dihalo compounds. Thus these different building blocks for TEMPO 2,2,6,6-Tetramethylpiperidyl-1-oxyl
the synthesis of various benzil derivatives are regarded as the TFA Trifluoroacetic acid
efficient toolkit for the synthetic chemists. THF Tetrahydrofuran
Keeping that perspective in mind, the synthesis of benzils TTN Thallium nitrate
using the new generation methods to the chemists is still
limited and challenging and further exploration into these Acknowledgements
aspects is highly desired. These efficient and greener techniques
like multicomponent one-pot, microwave irradiation, sonication, The authors are very grateful to DST, New Delhi for sanctioning
and electrochemical methods are need of an hour and provide the PURSE (Phase-II) program.
opportunities to the chemists for the structurally diverse
benzils. Furthermore, use of the greener solvents which
however can be recycled and reused can be concluded as a Conflict of Interest
successful and widely applicable addition to the toolkit of the
synthesis of benzils. The authors declare no conflict of interest.

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Keywords: benzils · benzoin · diarylalkynes (tolanes) · iodine/
DMSO-mediated oxidation · oxidation
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