Indium(III) bromide catalyzed direct azidation of α-hydroxyketones using TMSN3

Article abstract of DOI:10.1016/j.tet.2013.10.055

The direct catalytic azidation of 2-hydroxy-1,2,2-triarylethanones occurs at room temperature using 2 mol % of InBr₃ as Lewis acid and TMSN₃ as soluble azide source. 2-Azido-1,2,2-triarylethanones have been isolated in excellent yields. The role of aryl group and stereoelectronic factors indicate that the mechanism may involve the formation of a stable carbenium ion towards azidation.

Full text of DOI:10.1016/j.tet.2013.10.055

Tetrahedron 69 (2013) 10724e10732
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Indium(III) bromide catalyzed direct azidation of a-hydroxyketones
using TMSN3
,
,
a
Anil Kumar a y, Ramesh K. Sharma b, Tej V. Singh a , Paloth Venugopalan
*
a Department of Chemistry and Centre of Advanced Studies in Chemistry, Panjab University, Chandigarh 160014, India
b Sophisticated Analytical Instrumentation Facility, Panjab University, Chandigarh 160014, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 May 2013
Received in revised form 30 September 2013
Accepted 18 October 2013
Available online 23 October 2013
The direct catalytic azidation of 2-hydroxy-1,2,2-triarylethanones occurs at room temperature using
2 mol % of InBr3 as Lewis acid and TMSN3 as soluble azide source. 2-Azido-1,2,2-triarylethanones have
been isolated in excellent yields. The role of aryl group and stereoelectronic factors indicate that the
mechanism may involve the formation of a stable carbenium ion towards azidation.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Azidation
a
a
-Hydroxyketones
-Azidoketones
Indium(III) bromide
Azido trimethylsilane
1. Introduction
a
-azidation.7 Moreover, various sodium salts that result in azidation
with NaN3 pose considerable problems in homogeneity, rate and
workup of the reactions. To develop an economically and environ-
mentally benign protocol, direct azidation of alcohols is highly de-
sirable. However, the literature is devoid of such methods, except
a single example in which azidation of benzoin has been carried out
Azides represent an important class of compounds used for
various organic transformations as they are the potential pre-
cursors for the synthesis of amines, nitrenes and heterocyclic
compounds.1 Azides are also used for the synthesis of antituber-
culosis 1,2,3-triazoles via 1,3-dipolar cycloaddition using click
chemistry.2 The azide functional group exists in anti HIV-1 drugs
to obtain its
chiometricamounts of BF3$OEt2 as Lewis acid.8 Thus, attentionis still
awaiting a precise method to synthesize -azidoketones directly
from -hydroxyketones using catalytic quantity of Lewis acid.
a-azidoketone using NaN3 as azide source and stoi-
such as azidothymidine (AZT).3 In recent years,
a-azidoketones,
a
a unique family of azides, have become the subject of interest as
they are considered as versatile candidates for the synthesis of bi-
a
Recently, direct catalytic azidation of vinyl carbinols and allylic
alcohols has been reported to give corresponding azides using
a combination of BF3$OEt2/TMSN3 and AgOTf/TMSN3, respectively.9
Similarly, direct protocol for cyanation of various alcohols has been
given by Chen and co-workers using InBr3 and TMSCN.10 It has been
shown in these reactions that alcohols are activated by Lewis acids
to undergo nucleophilic substitution, and InBr3 proved to be an
effective catalyst for such activation. Considering the above-men-
tioned aspects, we hypothesized that it may be possible to activate
ologically active
tones can thus serve as building blocks for a variety of potentially
b a-Azidoke-
-amino alcohols4 and 1,3-oxazoles.5
useful classes of compounds, but the synthetic procedure of
azidoketones is very limited.
a-
The frequently used method for the preparation of
tones involves the nucleophilic substitution of the corresponding
substituted ketoneshavinga good leavinggroup withsodium azide.6
In such cases, preactivation of the -hydroxyketone as their halide,
a-azidoke-
a-
a
mesylate, triflate, tosylate, nosylate or phosphate is required before
the hydroxyl group of a-hydroxyketones for direct azidation with
Lewis acid such as InBr3. The prior transformation of alcohols to
better leaving groups can thus be completely eliminated. This will
provide an effective and general method to replace OH by N3 di-
rectly. Therefore, we report herein a direct catalytic azidation of a-
hydroxyketones and other alcohols using InBr3 as Lewis acid and
TMSN3 as soluble azide source.
* Corresponding author. Tel.: þ91 172 2534439; fax: þ91 172 2545074; e-mail
address: tvs@pu.ac.in (T.V. Singh).
y
Present address: University Institute of Engineering
University, Chandigarh 160014, India.
& Technology, Panjab
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.10.055

A. Kumar et al. / Tetrahedron 69 (2013) 10724e10732
10725
2. Results and discussion
(Scheme 3). After 1 h stirring, the TLC of the reaction mixture in-
dicated the presence of a single product, which was identified as 2-
azido-1,2,2-triphenylethanone (2d). The exclusive formation of 2d
leaving out any possibility of 2a, clearly demonstrates the crucial
role of the phenyl ring towards the azidation.
In order to investigate the above hypothesis that nucleophilic
substitution of hydroxyl group by azide ion ðNꢀ3 Þ can be carried out
directly from a-hydroxyketones, 2-hydroxy-1,2,-diphenylethanone
(1a) was selected (Scheme 1). To this a-hydroxyketone, 10 mol % of
O
O
InBr3 and 1.5 equiv of TMSN3 in CH2Cl2 at room temperature were
added. After 1 h stirring, the reactant underwent complete con-
version to the product, as analyzed by TLC. Subsequently the re-
action was quenched with water. After usual workup, the product
was identified as trimethylsilyl protected benzoin (2a) instead of 2-
azido-1,2-diphenylethanone on the basis of various spectroscopic
OTMS
OH
InBr3 (10 mol %)
1a
2a (not detected)
TMSN3 (1.5 equiv)
CH2Cl2, rt, 60 min
O
O
data including IR spectrum. A singlet for nine protons at d
0.02 in 1H
NMR confirms the presence of trimethylsilyl group. Similar results
were obtained during the azidation of furoin (1b) under similar
reaction conditions (Scheme 1). However, in the case anisoin (1c),
a small amount of its corresponding azide 2c was observed11
(Scheme 1). This outcome suggested that there must be some
electronic factors, which results in the azidation of anisoin.
N3
OH
2d (74%)
1d
Scheme 3. Reaction of equimolar mixture of benzoin (1a) and phenyl benzoin (1d)
with TMSN3 in the presence of InBr3.
O
O
InBr3 (10 mol %)
TMSN3 (1.5 equiv)
CH2Cl2, rt, 60 min
OH
O
OTMS
2a (91%)
1a
O
O
O
InBr3 (10 mol %)
TMSN3 (1.5 equiv)
CH2Cl2, rt, 60 min
O
OTMS
O
OH
1b
2b (44%)
OMe
OMe
InBr3 (10 mol %)
O
O
TMSN3 (1.5 equiv)
CH2Cl2, rt, 60 min
OH
1c
N3
MeO
MeO
2c (7%)
Scheme 1. Reaction of benzoin (1a), furoin (1b) and anisoin (1c) with TMSN3 in the presence of InBr3.
Interestingly, in the case of phenyl benzoin (1d), the azidation
Similarly, in order to study the effect of electron withdrawing
carbonyl group, azidation of 1,1,2-triphenylethanol (3) has been
carried out. Interestingly, the formation of corresponding azide 4
occurred in excellent yield (88%) besides 1,1,2-triphenylethene (5)
(yield 7%) as dehydration product (Scheme 4). This experiment
suggests that the exclusive interaction of the hydroxyl group with
InBr3 is responsible for the formation of a-azidoketones. Presence
of an electron withdrawing carbonyl group at the carbon bearing
OH group has minimal role in driving the azidation process.
occurred smoothly within 5 min under the same reaction conditions
(Scheme 2). The product was identified as 2-azido-1,2,2-
triphenylethanone (2d) on the basis of various spectroscopic data.
The presence of a sharp peak at wave number 2102 cmꢀ1 in the IR
spectrum confirms the presence of the azide group (eN3). The for-
mation of2dfrom1dsuggeststhatextraphenylgroupplaysadecisive
role in the azidation process. The introduction of one more phenyl
group at the carbon bearing hydroxyl group in 1a (resulting in 1d) not
only facilitates the direct azidation, but also reduces the time taken to
complete the reaction to greater extent.12 Analysis of the combined
outcome from Schemes 1 and 2 indicates that stereoelectronic factors
are playing significant role in driving the azidation reaction.
InBr3 (10 mol %)
Ph
H
Ph
Ph
Ph
N3
Ph
OH
Ph
Ph
TMSN3 (1.5 equiv)
CH2Cl2, rt, 5 min
Ph
Ph
3
4 ( 88 %)
5 (7 %)
Scheme 4. Reaction of 1,1,2-triphenylethanol with TMSN3 in the presence of InBr3.
O
O
InBr3 (10 mol %)
Based on the above observations, 2-hydroxy-1,2,2-
TMSN3 (1.5 equiv)
CH2Cl2, rt, 5 min
OH
N3
triphenylethanone13 (1d) was selected as a model
a-hydrox-
yketone to optimize the reaction conditions for azidation. The re-
action of 1d with 10 mol % of InBr3 and 1.5 equiv of TMSN3 in
various solvents at room temperature was studied (Table 1). Perusal
of Table 1 showed that the reaction occurred smoothly in CH2Cl2
within 5 min. The absence of product or its poor yield in the case of
acetone, acetonitrile, ether and THF may be due to their co-
ordinating behaviour with the catalyst. Further attention was paid
to test the efficiency of InBr3 as catalyst in CH2Cl2. For this purpose,
the catalytic amount of InBr3 was decreased to 0.5 mol % (entry 10),
2d (98%)
1d
Scheme 2. Reaction of phenyl benzoin (1d) with TMSN3 in the presence of InBr3.
To investigate the effect of phenyl group further, a synergistic
experiment was carried out. Both benzoin and phenyl benzoin in
equimolar quantities were treated with 1 equiv of TMSN3 and
10 mol % of InBr3 in dichloromethane at room temperature

10726
A. Kumar et al. / Tetrahedron 69 (2013) 10724e10732
Table 1
though it turned out to give lower yield (52%) in 5 h. Finally using
2 mol % of the catalyst, gave the -azidoketone equally well as that
Optimizationa of reaction conditions using InBr3 and TMSN3
a
O
O
of 10 mol % of InBr3 (Table 1, entry 8).
The successful azidation of 2-hydroxy-1,2,2-triphenylethanone,
which delineated the role of second phenyl group prompted us to
InBr3
Ph
Ph
N3
Ph
Ph
OH
TMSN3 (1.5 equiv)
CH2Cl2, rt
Ph
1d
Ph
investigate the azidation of other
a variety of other -hydroxyketones 1eem was treated with
2 mol % of InBr3 and 1.5 equiv of TMSN3 in CH2Cl2 (Table 2). All
a-hydroxyketones. Therefore,
2d
a
Entry
Solvent
InBr3 (mol %)
Time
Yieldb (%)
a
-
hydroxyketones were converted to the corresponding azides in
excellent yields within a short span under the optimized reaction
conditions. In the case of 1k (entry 8), a trace amount of corre-
sponding benzofuran derivative 6 was also formed during azidation
1
2
3
4
5
6
7
8
CH2Cl2
Acetone
Acetonitrile
Ether
THF
Chloroform
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
10
10
10
10
10
10
5
2
1
0.5
5 min
24 h
24 h
24 h
24 h
1 h
5 min
10 min
5 h
98
0
0
3
7
84
97
95
86
52
(Table 2, entry 8).14 In order to study the reactivity of
a-hydrox-
yketones having alkyl groups, azidation of
a-hydroxyketones 1n
(entry 11) and 1o (entry 12) was undertaken.15 However, they failed
to react. To observe the reactivity towards subtle variations in the
electronic effects, reaction with an additional methoxy group at
para-position of 1o (1p, entry 13) was carried out. The azidation did
take place in this case, though with poor yield (21%), clearly dem-
onstrating the role of electronic factors towards azidation. All new
9
10
5 h
a
Reactions were performed on 0.35 mmol scale of 2-hydroxy-1,2,2-
triphenylethanone in 5 mL of various solvents.
b
Isolated yields.
Table 2
a
-Azidation of various a
-hydroxyketones 1depa
O
O
R3
R3
N3
InBr3 (2 mol %)
R1
R1
R2
1d-p
R2
OH
TMSN3 (1.5 equiv)
CH2Cl2, rt
2d-m, 2p
Entry
1
a
-Hydroxyketone
a
-Azidoketone
Time (min)
10
Yieldb (%)
O
O
Ph
Ph
N3
Ph
Ph
95
OH
Ph
1d
Ph
2d
O
O
2
3
Ph
Ph
10
13
98
94
Ph
Ph
Me
Me
N3
OH
1e
2e
O
O
Ph
Ph
Me
Me
Ph
Ph
Me
Me
Ph
Ph
OH
OH
N3
1f
2f
O
O
4
5
6
15
50
12
96
96
91
Ph
Ph
N3
1g
2g
O
O
Ph
Ph
Ph
Ph
OMe
OMe
N3
OH
1h
2h
OMe
OMe
O
O
Ph
Ph
Ph
Ph
OH
N3
1i
2i

A. Kumar et al. / Tetrahedron 69 (2013) 10724e10732
10727
Table 2 (continued )
Entry
a
-Hydroxyketone
a
-Azidoketone
Time (min)
22
Yieldb (%)
Me
Me
O
O
7
93
Ph
Ph
N3
2j
OH
Me
Me
1j
O
O
8
9
20
15
91c
Ph
Ph
Ph
Ph
OH
1k
N3
2k
F
F
O
O
97
Ph
Ph
OH
N3
F
F
1l
2l
O
O
Ph
Ph
N3
10
11
30
86
Ph
Ph
OH
MeO
MeO
1m
2m
O
Me
OH
NRd
120
d
Me
Me
1n
O
Me
12
NRd
120
120
d
OH
Me
1o
OMe
OMe
O
O
13
21
Me
Me
OH
N3
Me
1p
Me
2p
a
Reactions were performed on 0.70 mmol scale of
Isolated yields.
a-hydroxyketones in CH2Cl2 (5 mL) containing InBr3 (2 mol %) and TMSN3 (1.5 equiv).
b
c
Trace amount of 3-(1-naphthyl)-2-phenyl benzofuran (6) was also formed (see Experimental).14
d
No reaction.
compounds have been characterized using various spectral data
(see Experimental).
facile loss of both N3 as well as CO group (Scheme 5). It may be
due to the loss of CO from B to give more stable triaryl methyl
cation (C).
The IR spectra of a-azidoketones showed absorption bands for
the azido group in the range of 2102e2104 cmꢀ1. The carbonyl
stretching frequencies in all the ketones are characteristics of
conjugative aryl ketones in the range of 1678e1694 cmꢀ1. Com-
pound 2d absorbs at 1694 cmꢀ1 and 2m at 1678 cmꢀ1. The lowest
frequency for the carbonyl at 1678 cmꢀ1 is the result of a prominent
resonance effect of p-OMe group present in the phenyl ring in 2m.
O
Ar3
Ar2
O
Ar3
N3
Ar3
Ar2
Ar1
Ar1
Ar1
Ar2
(M+)
(M+-N3-CO)
(M+-N3)
1H NMR of all ketones displayed signals in the range of
d 6.69e7.86
A
B
C
for aromatic protons and peaks for other substituents at expected
Scheme 5. ESI mass fragmentation of 2-azido-1,2,2-triarylethanones.
chemical shift values. Compounds 2deg and 2iem showed ortho
aromatic protons (2H) downfield in the range of
d
7.64e7.86 due to
Keeping in view that 2-hydroxy-1,2,2-triphenylethanone (1d)
has benzoyl and benzhydrol moieties, it was of interest to explore
our present method for the azidation of alcohols without benzoyl
moiety such as benzyl alcohol and benzhydrol. In addition, these
two systems will help us to extrapolate the role of the phenyl ring
anisotropic effect of the carbonyl group whereas in case of 2h, it
seems that ortho protons are merged into multiplets with other
aromatic protons. 13C NMR spectra showed expected chemical
shifts in the range of
d 194.8e198.2 for carbonyl carbons. The mo-
lecular ion peak (A) in ESI mass spectra was absent in all
a
-azido-
in benzhydrol, and eCOAr in a-hydroxyketones for the azidation.
ketones 2dem (Scheme 5). The base peak appeared at m/z MþꢀN3
(B) in 2h, 2k and 2p by the loss of azido group (Scheme 5). Other
Therefore, benzyl alcohol (1q) and 1,1-diphenylmethanol (1r,
Table 3, entry 1) were also treated with InBr3 and TMSN3. In-
terestingly, 1-azido-1,1-diphenylmethane (2r) was formed from
a
-azidoketones showed base peak at m/z MþꢀN3ꢀCO (C) by the

10728
A. Kumar et al. / Tetrahedron 69 (2013) 10724e10732
Table 3
Azidation of 1,1-diarylmethanolsa
OH
Ar2
1r-w
N3
InBr3 (2 mol %)
Ar1
Ar1
Ar2
TMSN3 (1.5 equiv)
CH2Cl2, rt
2r-w
Entry
1
Alcohol
Product
Time (min)
5
Yieldb (%)
97
OH
N3
Ph
Ph
Ph
Ph
2r
1r
OH
Ph
N3
2
5
55
30
98
89
90
Ph
Ph
1s
2s
MeO
MeO
O2N
OH
N3
3
4
Ph
1t
2t
O2N
OH
N3
F
F
F
F
1u
2u
OH
N3
5
6
Ph
Ph
25
10
88
93
1v
2v
F3C
Me
F3C
Me
OH
N3
Ph
Ph
1w
2w
a
Reactions were performed on 1 mmol scale of 1,1-diarylmethanol in CH2Cl2 (5 mL) using 1.5 equiv of TMSN3.
Isolated yields obtained after flash chromatography.
b
1,1-diphenylmethanol in excellent yield within 5 min. This result
a racemic mixture of 1-azido-1-(4-nitrophenyl)-1-phenylmethane
(2t). The formation of a carbenium ion as an intermediate may
thus be considered as one of the possibilities towards azidation. The
formation of a trace amount of 1,1,2-triphenylethene (5) via elim-
ination of water from 3 also falls in the above line. Similarly, the
isolation of 3-(1-naphthyl)-2-phenyl benzofuran (6) as a rear-
suggested that there is not much effect of the eCOAr group present
at the carbon bearing the hydroxyl group in a
-hydroxyketones.16
The reaction did not occur in the case of benzyl alcohol, which
also highlights the role of phenyl group (see Experimental). Azi-
dation of various benzhydrols 1sew having electron withdrawing
group (EWG) and electron donating group (EDG) has been carried
out to study the electronic effects during azidation (Table 3). It has
been found that the reaction of benzhydrol having electron with-
drawing nitro group (1t, Table 3, entry 3) proceeds slowly. All other
benzhydrols gave corresponding azides within a short period of
time. Benzhydryl azides have been characterized by various spec-
tral data (see Experimental). The IR spectra of compounds 2rew
showed absorption bands for the azido group in the range of
2097e2102 cmꢀ1. 1H NMR spectra of azides 2rew displayed char-
rangement product in
a
-hydroxyketone 1k indicates the in-
termediacy of an
a
-ketocarbenium ion.16
3. Conclusions
An economically and environmentally benign protocol for
the azidation of various alcohols to give their corresponding
azides has been uncovered. Various
a-hydroxyketones and 1,1-
diarylmethanols are converted to -azidoketones and 1-azido-1,1-
a
acteristic singlet at
d
5.55e5.72 (s, 1H) for benzhydrylic protons and
diarylmethanes, respectively, using TMSN3 as a soluble azide
source and catalytic amount of InBr3 as Lewis acid. There is no need
multiplets at 6.79e8.15 for the aromatic protons.
d
It is worth linking all the information obtained from the above
experiments that are useful for predicting the mechanism. The
azidation of benzoin (2-hydroxy-1,2-diphenylethanone) under
identical conditions does not take place rather it gives the trime-
thylsilyl protected benzoin (TMS ether). The azidation of phenyl
benzoins (2-hydroxy-1,2,2-triarylethanones), however, occurs
smoothly. These experiments indicate that substitution of OH at
carbon bearing two phenyl groups occurs with TMSN3 where N3ꢀ
acts as nucleophile. This finds support by the azidation of various
1,1-diarylmethanols. The azidation of enantioenriched 1-(4-
nitrophenyl)-1-phenylmethanol (1t), however, results in
for the preactivation of
a
-hydroxyketones prior to azidation. The
formation of -azidoketones from
a
a-hydroxyketones except ben-
zoin (1a) and furoin (1b) indicates the crucial role of aryl group and
stereoelectronic factors towards azidation. The successful azidation
of benzhydrols 1rew and 1,1,2-triphenylethanol (3) suggests that
the presence of carbonyl group in a-hydroxyketones has a minimal
role in driving the azidation process. Thus, through this protocol, an
efficient strategy for the synthesis of an important class of organic
azides has been put forward. Further work is to discover the cata-
lytic system and/or soluble azide source for enantioselective azi-
dation of a-hydroxyketones.

A. Kumar et al. / Tetrahedron 69 (2013) 10724e10732
10729
4. Experimental
6.25e6.29 (2H, m, ArH), 5.68 (1H, s, CH), 0.06 (9H, s, 3ꢁCH3); 13C
NMR (100.53 MHz, CDCl3): 184.5, 151.3, 150.2, 147.0, 142.9, 120.2,
112.2, 110.7, 109.1, 72.1, ꢀ0.1.
4.1. Equipments/chemicals
Melting points were recorded in open capillaries and are un-
corrected. IR spectra were recorded with Perkin Elmer IR 1800
spectrophotometer. A thin film or KBr pellets were used to record
the FTIR spectra. 1H NMR and 13C NMR spectra were recorded in
CDCl3 solutions on Bruker Avance II 400 NMR spectrometer oper-
4.4. 2-Azido-1,2-bis(4-methoxyphenyl) ethanone21 (2c)
A solution of 2-hydroxy-1,2-bis(4-methoxyphenyl) ethanone, 1c
(500 mg, 1.84 mmol) in dry CH2Cl2 (5 mL) and TMSN3 (317 mg,
2.76 mmol) were placed in a 25 mL round-bottom flask fitted with
guard tube. InBr3 (66 mg, 0.18 mmol) was added to this reaction
mixture. The contents were stirred at room temperature for 60 min.
The reaction was quenched with water. The product was extracted
with CH2Cl2 (3ꢁ15 mL), washed with 10% Na2CO3 (20 mL), water
(20 mL) and dried over anhydrous Na2SO4. The solvent was re-
moved under reduced pressure to give brownish oil. Purification by
flash chromatography afforded the product 2c as light yellowish oil.
Yield: 7%; IR (neat): 2933, 2839, 2095, 1677, 1595, 1573, 1508, 1459,
1441, 1305, 1251, 1166, 1027 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.77
(2H, d, J¼8.9 Hz, ArH), 7.22 (2H, d, J¼8.7 Hz, ArH), 6.82 (2H, d,
J¼8.7 Hz, ArH), 6.77 (2H, d, J¼8.9 Hz, ArH), 5.55 (1H, s, CH), 3.73
(3H, s, OCH3), 3.69 (3H, s, OCH3); 13C NMR (100.53 MHz, CDCl3):
192.9, 163.8, 160.2, 132.3, 131.2, 129.6, 127.2, 126.2, 114.8, 113.9, 67.1,
55.4, 55.2.
ating at 400 MHz and 100.62 MHz, respectively. Chemical shifts (d)
are reported in parts per million downfield from tetramethyl silane
as internal standard. Coupling constants (J) are in hertz (Hz).
Multiplicity of the signal is defined as ‘s’ (singlet), ‘d’ (doublet), ‘t’
(triplet), ‘q’ (quartet), ‘m’ (multiplet). Mass spectra were obtained
with Waters Q-ToF Micro mass spectrometer running under Mass
Lynx version 4.0 software and equipped with an ESI source. Relative
intensities are given in parentheses. TLC analyses were performed
using aluminium backed plates pre-coated with silica gel contain-
ing fluorescent material and examining them under UV light
(l¼254 and 355 nm). Azidotrimethylsilane (TMSN3), indium(III)
bromide, 3-hydroxy-3-methyl-2-butanone, benzil and substituted
benzils were purchased from SigmaeAldrich and used as such
without purification. 2-Hydroxy-1,2,2-triarylethanones were pre-
pared by reacting the appropriate Grignard reagent with benzil or
substituted benzil. Dichloromethane (DCM) was dried over phos-
phorus pentoxide and distilled before use. HPLC analysis for com-
pound 1t was performed on Chiralcel OD column by using hexane/
ethylacetate (95:5) as eluent with flow rate of 0.5 mL/min. While
for 2t, HPLC analysis was performed on Chiralpak ASH column by
using hexane/ethyl acetate (95:2) as eluent with flow rate of
0.5 mL/min.17 Flash chromatography was performed by using
4.5. 1-Azido-1,1,2-triphenylethane (4)
A solution of 1,1,2-triphenylethanol (3) (200 mg, 0.73 mmol) in
dry CH2Cl2 (5 mL) and TMSN3 (127 mg, 1.09 mmol) were placed in
a 25 mL round-bottom flask fitted with guard tube. InBr3 (5.0 mg,
0.014 mmol) was added to this reaction mixture. The contents were
stirred at room temperature for 10 min. The reaction was quenched
with water. The product was extracted with CH2Cl2 (3ꢁ15 mL),
washed with 10% Na2CO3 (20 mL), water (20 mL) and dried over
anhydrous Na2SO4. The solvent was removed under reduced pres-
sure to give brownish oil. Purification by flash chromatography
afforded the product 4. White solid. Mp: 86e87 ꢂC. Yield: 88%; Rf
(5% hexane/ethylacetate) 0.70; IR (KBr): 3060, 3029, 2925, 2105,
40e63 mm silica gel (230e400 mesh) and applying nitrogen pres-
sure from the top of the column.18
4.2. 1,2-Diphenyl-2-trimethylsilanyloxyethanone19 (2a)
A solution of 2-hydroxy-1,2-diphenyl ethanone, 1a (200 mg,
0.94 mmol) in dry CH2Cl2 (5 mL) and TMSN3 (163 mg, 1.41 mmol)
were placed in a 25 mL round-bottom flask fitted with guard tube.
InBr3 (17 mg, 0.094 mmol) was added to this reaction mixture. The
contents were stirred at room temperature for 60 min. The reaction
was quenched with water. The product was extracted with CH2Cl2
(3ꢁ15 mL), washed with 10% Na2CO3 (20 mL), water (20 mL) and
dried over anhydrous Na2SO4. The solvent was removed under re-
duced pressure to give brownish oil. Purification by flash chroma-
tography afforded the product 2a as white solid. Mp: 80e81 ꢂC.
Yield: 91%; 1H NMR (400 MHz, CDCl3): 7.89 (2H, d, 3J¼7.1 Hz, ArH),
7.35e7.39 (3H, m, ArH), 7.21e7.27 (4H, m, ArH), 7.15e7.17 (1H, m,
ArH), 5.73 (1H, s, CH), 0.02 (9H, s, 3ꢁCH3); 13C NMR (100.53 MHz,
CDCl3): 198.6, 138.9, 134.7, 132.9, 129.7, 128.7, 128.3, 128.0, 126.4,
79.5, 0.1.
1599, 1584, 1495, 1445, 1376, 1318, 1257, 1078 cmꢀ1 1H NMR
;
(400 MHz, CDCl3): 7.15e7.24 (10H, m, ArH), 6.99e7.08 (3H, m, ArH),
6.64e6.67 (2H, m, ArH), 3.58 (2H, s, CH2); 13C NMR (100.53 MHz,
CDCl3): 142.6, 135.6, 130.5, 128.1, 127.6, 127.5, 126.5, 73.2, 45.0;
HRMS (ESI): calcd for C20H17 (MþꢀN3) m/z 257.1325. Found
257.1362.
4.6. General procedure for the preparation of a-azidoketones
A solution of 2-hydroxy-1,2,2-triarylethanones, 1dep (200 mg,
0.58e0.66 mmol) in dry CH2Cl2 (5 mL) and TMSN3 (1.5 equiv) were
placed in a 25 mL round-bottom flask (RBF) fitted with guard tube.
InBr3 (2 mol %) was added to this reaction mixture. The contents
were stirred at room temperature and the progress of reaction was
monitored by TLC analyses. After stirring the contents for appro-
priate time period, the reaction was quenched with water. The
product was extracted with CH2Cl2 (3ꢁ15 mL), washed with 10%
Na2CO3 (20 mL), water (20 mL) and dried over anhydrous Na2SO4.
The solvent was removed under reduced pressure to give brownish
oil. Purification by flash chromatography afforded the products
2dem, 2p and 6.
4.3. 1,2-Bis(2-furyl)-2-trimethylsilanyloxyethanone20 (2b)
A solution of 2-hydroxy-1,2-bis(2-furyl) ethanone, 1b (200 mg,
1.04 mmol) in dry CH2Cl2 (5 mL) and TMSN3 (180 mg, 1.56 mmol)
were placed in a 25 mL round-bottom flask fitted with guard tube.
InBr3 (37 mg, 0.104 mmol) was added to this reaction mixture. The
contents were stirred at room temperature for 60 min. The reaction
was quenched with water. The product was extracted with CH2Cl2
(3ꢁ15 mL), washed with 10% Na2CO3 (20 mL), water (20 mL) and
dried over anhydrous Na2SO4. The solvent was removed under re-
duced pressure to give brownish oil. Purification by flash chroma-
tography afforded the product 2b as white solid. Yield: 44%; 1H
NMR (400 MHz, CDCl3): 7.53 (1H, d, J¼1.3 Hz, ArH), 7.36 (1H, d,
J¼3.6 Hz, ArH), 7.31 (1H, d, J¼1.2 Hz, ArH), 6.45e6.46 (1H, m, ArH),
4.6.1. 2-Azido-1,2,2-triphenylethanone (2d). White solid. Mp:
55e56 ꢂC. Yield: 95%; Rf (10% hexane/ethylacetate) 0.53; IR (KBr):
3054, 3032, 2102, 1694, 1594, 1492, 1445, 1254, 1203, 1171,
1032 cmꢀ1 1H NMR (400 MHz, CDCl3): 7.84e7.86 (2H, m, ArH),
;
d
7.33e7.50 (13H, m, ArH); 13C NMR (100.53 MHz, CDCl3): 197.1,
138.7, 135.7, 132.7, 130.3, 128.7, 128.6, 128.3, 128.1, 80.3; ESI-MS: 272
(10.7), 271 (58.8, MþꢀN3), 244 (16.8), 243 (100, MþꢀN3ꢀCO), 228

10730
A. Kumar et al. / Tetrahedron 69 (2013) 10724e10732
(5.2), 165 (23.1%); HRMS (ESI): calcd for C20H15O (MþꢀN3) m/z
IR (thin film): 3057, 3028, 2953, 2922, 2867, 2103, 1681, 1605, 1570,
1510, 1492, 1446, 1408, 1249, 1182 cmꢀ1 1H NMR (400 MHz,
271.1117. Found 271.1117.
;
CDCl3): 7.65e7.67 (2H, m, ArH), 7.24e7.32 (5H, m, ArH), 7.09e7.16
(4H, m, ArH), 7.02 (2H, d, J¼8 Hz, ArH), 2.27 (3H, s, CH3), 2.24 (3H,
s, CH3); 13C NMR (100.53 MHz, CDCl3): 196.4, 143.5, 139.0, 138.4,
135.8, 132.9, 130.5, 129.3, 128.7, 128.5, 128.4, 128.3, 128.2, 80.2,
21.6, 21.1; ESI-MS: 364 (19.9, MþNa), 301 (20.3), 299 (57.2,
MþꢀN3), 272 (24.9), 271 (100, MþꢀN3ꢀCO), 196 (10), 79 (7.6%);
HRMS (ESI): calcd for C22H19O (MþꢀN3) m/z 299.1430. Found
299.1463.
4.6.2. 2-Azido-2-(2-methylphenyl)-1,2-diphenylethanone
(2e). Colourless oil. Yield: 98%; Rf (10% hexane/ethylacetate) 0.54;
IR (thin film): 3061, 3022, 2973, 2869, 2103, 1681, 1596, 1578, 1485,
1445, 1241,1182 cmꢀ1. 1H NMR (400 MHz, CDCl3): 7.65e7.67 (2H, m,
ArH), 7.43e7.46 (2H, m, ArH), 7.31e7.40 (4H, m, ArH), 7.17e7.25 (4H,
m, ArH), 7.01e7.05 (1H, m, ArH), 6.77 (1H, d, 3J¼8 Hz, ArH), 2.20
(3H, s, CH3); 13C NMR (100.53 MHz, CDCl3): 197.0, 137.8, 137.6, 137.5,
135.9, 132.5, 132.1, 130.2, 129.8, 129.0, 128.9, 128.6, 128.2, 127.9,
125.6, 80.7, 21.8; ESI-MS: 350 (5.4, MþNa), 286 (10.3), 285 (45,
MþꢀN3), 258 (20.4), 257 (100, MþꢀN3ꢀCO), 196 (12), 179 (20.2),
165 (5.8), 105 (4.7%); HRMS (ESI): calcd for C21H17O (MþꢀN3) m/z
285.1274. Found 285.1276.
4.6.8. 2-Azido-2-(1-naphthyl)-1,2-diphenylethanone
(2k). White
solid. Mp: 104e105 ꢂC. Yield: 91%; Rf (10% hexane/ethylacetate)
0.51; IR (KBr): 3059, 2954, 2926, 2104, 1682, 1596, 1578, 1493,
1366, 1240, 1181 cmꢀ1 1H NMR (400 MHz, CDCl3): 7.84 (1H, d,
;
J¼8.4 Hz, ArH), 7.76e7.80 (2H, m, ArH), 7.70e7.72 (2H, m, ArH),
7.46e7.49 (2H, m, ArH), 7.31e7.41 (6H, m, ArH), 7.14e7.27 (3H, m,
ArH), 7.02 (1H, d, J¼7.2 Hz, ArH); 13C NMR (100.53 MHz, CDCl3):
197.4, 137.7, 136.0, 135.6, 134.5, 132.6, 130.9, 130.5, 130.3, 129.2,
129.1, 128.9, 128.8, 128.4, 128.0, 126.5, 126.1, 125.8, 124.4, 80.8;
ESI-MS: 386 (12.8, MþNa), 322 (28.7), 321 (100, MþꢀN3),
294 (6), 293 (15, MþꢀN3ꢀCO), 215 (17.6), 179 (5), 105 (4.4%);
HRMS (ESI): calcd for C23H17 (MþꢀN3ꢀCO) m/z 293.1325. Found
293.1381.
4.6.3. 2-Azido-2-(3-methylphenyl)-1,2-diphenylethanone
(2f). Colourless oil. Yield: 94%; Rf (10% hexane/ethylacetate) 0.57; IR
(thin film): 3060, 2922, 2860, 2103, 1681, 1596, 1578, 1488, 1446,
1230,1182 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.72e7.74 (2H, m, ArH),
7.15e7.38 (9H, m, ArH), 7.07e7.10 (3H, m, ArH), 2.25 (3H, s, CH3); 13
C
NMR (100.53 MHz, CDCl3): 197.1, 138.8, 138.5, 138.4, 135.8, 132.6,
130.2, 129.4, 128.8, 128.6, 128.5, 128.4, 128.2, 128.0, 125.3, 80.3, 21.6;
ESI-MS: 350 (14, MþNa), 286 (12.8), 285 (56.6, MþꢀN3), 258 (20.5),
257 (100, MþꢀN3ꢀCO), 196 (18.8), 179 (17.2), 165 (4.1%); HRMS
(ESI): calcd for C21H17O (MþꢀN3) m/z 285.1274. Found 285.1279.
4.6.9. 3-(1-Naphthyl)-2-phenyl benzofuran (6). White solid. Mp:
92e93 ꢂC (lit.14b mp 94e95 ꢂC). Yield: 63%; Rf (10% hexane/ethyl-
acetate) 0.57; 1H NMR (400 MHz, CDCl3): 7.83 (1H, d, J¼8.1 Hz,
ArH), 7.63e7.68 (2H, m, ArH), 7.44e7.48 (8H, m, ArH), 7.28e7.32
(1H, m, ArH), 7.14e7.21 (4H, m, ArH); 13C NMR (100.53 MHz, CDCl3):
151.4, 150.1, 134.7, 131.0, 130.9, 130.6, 129.4, 128.9, 128.4, 128.3,
128.2, 127.8, 126.2, 126.0, 124.2, 123.6, 123.1, 119.5, 112.2.
4.6.4. 2-Azido-2-(4-methylphenyl)-1,2-diphenylethanone
(2g). Colourless oil. Yield: 96%; Rf (10% hexane/ethylacetate) 0.60;
IR (thin film): 3058, 3027, 2921, 2102, 1682, 1596, 1573, 1510, 1492,
1446, 1237, 1183 cmꢀ1 1H NMR (400 MHz, CDCl3): 7.72e7.75 (2H,
;
m, ArH), 7.36e7.38 (1H, m, ArH), 7.21e7.33 (7H, m, ArH), 7.10e7.16
(4H, m, ArH), 2.28 (3H, s, CH3); 13C NMR (100.53 MHz, CDCl3): 197.1,
138.8, 138.5, 135.7, 135.6, 132.6, 130.2, 129.3, 128.6, 128.5, 128.3,
128.2, 128.0, 80.2, 21.1; ESI-MS: 350 (15.1, MþNa), 286 (12.3), 285
(55.9, MþꢀN3), 258 (21.5), 257 (100, MþꢀN3ꢀCO), 196 (11.3), 179
(14.7), 165 (3.4%); HRMS (ESI): calcd for C20H17 (MþꢀN3ꢀCO) m/z
257.1325. Found 257.1340.
4.6.10. 2-Azido-1,2-bis(2-fluorophenyl)-2-phenylethanone
(2l). Colourless oil. Yield: 97%; Rf (10% hexane/ethylacetate) 0.56;
IR (thin film): 3067, 2926, 2104, 1688, 1597, 1504, 1447, 1408,
1233, 1159 cmꢀ1 1H NMR (400 MHz, CDCl3): 7.80e7.84 (2H, m,
;
ArH), 7.31e7.37 (3H, m, ArH), 7.25e7.30 (2H, m, ArH), 7.18e7.22
(2H, m, ArH), 6.99e7.03 (2H, m, ArH), 6.91e6.99 (2H, m, ArH); 13
C
4.6.5. 2-Azido-2-(2-methoxyphenyl)-1,2-diphenylethanone
(2h). White solid. Mp: 83e84 ꢂC. Yield: 96%; Rf (10% hexane/eth-
ylacetate) 0.48; IR (KBr): 3061, 2936, 2837, 2103, 1681, 1597, 1486,
NMR (100.53 MHz, CDCl3): 194.9, 165.2 (d), 162.5 (d), 138.3, 134.5
(d), 133.2 (d), 131.4 (d), 130.3 (d), 128.9, 128.8, 127.9, 115.5 (d),
115.3 (d), 79.5; ESI-MS: 372 (6.4, MþNa), 308 (11.9), 307 (47.3,
MþꢀN3), 280 (24.5), 279 (100, MþꢀN3ꢀCO), 200 (69.7), 123
(44.3%); HRMS (ESI): calcd for C20H13F2O (MþꢀN3) m/z 307.0929.
Found 307.0927.
1446, 1247, 1180 cmꢀ1 1H NMR (400 MHz, CDCl3): 7.57e7.63 (4H,
;
m, ArH), 7.31e7.38 (4H, m, ArH), 7.22e7.28 (3H, m, ArH), 6.86 (1H, d,
3J¼8 Hz, ArH), 6.79e6.83 (1H, m, ArH), 6.69e6.72 (1H, m, ArH), 3.64
(3H, s, OCH3); 13C NMR (100.53 MHz, CDCl3): 197.4, 156.3, 137.0,
136.9, 131.8, 130.4, 129.8, 129.3, 129.2, 128.7, 128.4, 128.2, 127.8,
120.7, 111.5, 78.1, 55.4; ESI-MS: 366 (23.6, MþNa), 302 (22.8), 301
(100, MþꢀN3), 274 (14.7), 273 (66.7, MþꢀN3ꢀCO), 210 (12.3), 195
(10.5), 167 (26.8%); HRMS (ESI): calcd for C21H17O2 (MþꢀN3) m/z
301.1223. Found 301.1228.
4.6.11. 2-Azido-1-(4-methoxyphenyl)-2,2-diphenylethanone
(2m). Colourless oil. Yield: 86%; Rf (10% hexane/ethylacetate)
0.50; IR (thin film): 3060, 3033, 2932, 2839, 2103, 1678, 1599,
1573, 1509, 1493, 1446, 1420, 1310, 1246, 1172 cmꢀ1 1H NMR
;
(400 MHz, CDCl3): 7.80 (2H, d, J¼7.8 Hz, ArH), 7.24e7.32 (10H, m,
ArH), 6.70 (2H, d, J¼7.8 Hz, ArH), 3.70 (3H, s, OCH3); 13C NMR
(100.53 MHz, CDCl3): 194.8, 163.1, 139.0, 133.0, 128.6, 128.4, 128.3,
127.9, 113.3, 80.1, 55.4; ESI-MS: 366 (6.0, MþNa), 302 (6.5), 301
(29, MþꢀN3), 274 (20.4), 273 (100, MþꢀN3ꢀCO), 195 (11.2), 135
(4.2%); HRMS (ESI): calcd for C20H17O (MþꢀN3ꢀCO) m/z 273.1274.
Found 273.1279.
4.6.6. 2-Azido-2-(4-methoxyphenyl)-1,2-diphenylethanone
(2i). Colourless oil. Yield: 91%. Rf (10% hexane/ethylacetate) 0.41; IR
(thin film): 3060, 3035, 2956, 2837, 2484, 2103, 1681, 1606, 1579,
1493, 1445, 1372, 1300, 1253, 1181, 1078 cmꢀ1 1H NMR (400 MHz,
;
CDCl3): 7.64 (2H, d, J¼7.5 Hz, ArH), 7.13e7.30 (8H, m, ArH), 7.08 (2H,
d, J¼6.8 Hz, ArH), 6.75 (2H, d, J¼6.8 Hz, ArH), 3.65 (3H, s, OCH3); 13
C
NMR (100.53 MHz, CDCl3): 198.2, 159.5, 138.9, 135.7, 132.6, 130.6,
130.2, 129.7, 128.6, 128.5, 128.2, 128.0, 113.9, 80.1, 55.3; ESI-MS: 366
(11.9, MþNa), 302 (18), 301 (82.5, MþꢀN3), 274 (21.2), 273 (100,
4.6.12. 3-Azido-3-(4-methoxyphenyl)-2-butanone (2p). Light yel-
lowish oil. Yield: 21%; Rf (5% hexane/ethylacetate) 0.45; IR (thin
film): 2936, 2838, 2091, 1718, 1607, 1581, 1509, 1462, 1375, 1354,
1301, 1246, 1179, 1092, 1029 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.21
(2H, d, J¼6.7 Hz, ArH), 6.82 (2H, d, J¼6.7 Hz, ArH), 3.71 (3H, s,
OCH3), 1.98 (3H, s, CH3), 1.69 (3H, s, CH3); 13C NMR (100.53 MHz,
CDCl3): 204.6, 159.6, 130.2, 127.0, 114.3, 73.2, 55.2, 24.9, 21.6; ESI-
MS: 242 (6.3, MþNa), 178 (13.0), 177 (100, MþꢀN3), 163 (22.5),
MþꢀN3ꢀCO), 212 (8.6), 195 (6.8%); HRMS (ESI): calcd for C20H17
(MþꢀN3ꢀCO) m/z 273.1274. Found 273.1255.
O
4.6.7. 2-Azido-1,2-bis(4-methylphenyl)-2-phenylethanone
(2j). Colourless oil. Yield: 93%. Rf (10% hexane/ethylacetate) 0.70;

A. Kumar et al. / Tetrahedron 69 (2013) 10724e10732
10731
149 (79.3, MþꢀN3ꢀCO), 126 (11.9), 121 (7.3%); HRMS (ESI): calcd for
CH3); 13C NMR (100.53 MHz, CDCl3): 139.8,137.9,136.6,129.4,128.7,
128.0, 127.4, 127.3, 68.4, 21.1; HRMS (ESI): calcd for C14H13 (MþꢀN3)
m/z 181.1012. Found 181.1003.
C
11H13O2 (MþꢀN3) m/z 177.0910. Found 177.0913.
4.7. General procedure for the preparation of 1-azido-1,1-
diaryl methane
Acknowledgements
A
solution of 1,1-diarylmethanol, 1rew (200 mg,
We are grateful to the University Grants Commission (UGC),
New Delhi, for providing financial assistance (36-194/2008-SR).
One of the authors (A.K.) thanks to the Council of Scientific and
Industrial Research (CSIR), New Delhi, for senior research fellow-
ship (09/135 (0604)/2010-EMR-I). We sincerely thank Avtar Singh,
Munish Kumar and Anoop Patyal (SAIF, Panjab University, Chan-
digarh) for collection of spectral data.
0.80e1.08 mmol) in dry CH2Cl2 (5 mL) and TMSN3 (1.5 equiv) were
placed in a 25 mL round-bottom flask fitted with guard tube. InBr3
(2 mol %) was added to this reaction mixture. The contents were
stirred at room temperature and the progress of reaction was
monitored by TLC analyses. After stirring the contents for appro-
priate time period, the reaction was quenched with water. The
product was extracted with CH2Cl2 (3ꢁ15 mL), washed with 10%
Na2CO3 (20 mL), water (20 mL) and dried over anhydrous Na2SO4.
The solvent was removed under reduced pressure to give brownish
oil. Purification by flash chromatography afforded the products
2rew.
Supplementary data
1H NMR and 13C NMR spectra of all new compounds. Supple-
mentary data associated with this article can be found in the online
version, at http://dx.doi.org/10.1016/j.tet.2013.10.055.
4.7.1. 1-Azido-1,1-diphenylmethane22 (2r). Colourless oil. Yield:
97%; Rf (5% hexane/ethylacetate) 0.75; IR (thin film): 3062, 3029,
2098, 1601, 1493, 1453, 1238, 1182, 1079 cmꢀ1; 1H NMR (400 MHz,
CDCl3): 7.06e7.22 (10H, m, ArH), 5.55 (1H, s, CH); 13C NMR
(100.53 MHz, CDCl3): 139.5, 128.7, 128.4, 128.1, 127.4, 127.3, 68.5.
References and notes
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88, 297e368; (d) Labb, E. G. Chem. Rev. 1969, 69, 345e363.
4.7.2. 1-Azido-1-(4-methoxyphenyl)-1-phenylmethane
(2s). Colourless oil. Yield: 98%; Rf (5% hexane/ethylacetate) 0.57; IR
(thin film): 3061, 3030, 3003, 2956, 2836, 2098, 1610, 1512, 1493,
1453, 1249, 1174, 1033 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.20e7.28
(5H, m, ArH), 7.12e7.14 (2H, d, J¼6.6 Hz, ArH), 6.79 (2H, d, J¼6.6 Hz,
ArH), 5.58 (1H, s, CH), 3.70 (3H, s, OCH3); 13C NMR (100.53 MHz,
CDCl3): 159.3, 139.9,131.7, 128.8, 128.6, 127.9, 127.2, 114.0, 68.1, 55.3;
HRMS (ESI): calcd for C14H13O (MþꢀN3) m/z 197.0961. Found
197.0936.
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753e757; (b) Hong-Wang, Z.; Coats, S. J.; Bondada, L.; Amblard, F.; Detorio, M.;
Asif, G.; Fromentin, E.; Solomon, S.; Obikhod, A.; Whitaker, T.; Sluis-Cremer, N.;
Mellors, J. W.; Schinazi, R. F. Bioorg. Med. Chem. Lett. 2010, 20, 60e64; (c)
Agarwal, H. K.; Doncel, G. F.; Parang, K. Tetrahedron Lett. 2008, 49, 4905e4907;
(d) Kumar, R.; Sharma, N.; Nath, M.; Saffran, H. A.; Tyrrell, D. L. J. J. Med. Chem.
2001, 44, 4225e4229.
4. (a) Ito, Y.; Sawamura, M.; Hayashi, T. Tetrahedron Lett. 1988, 29, 239e240; (b)
Gurjar, M. K.; Path, V. J.; Yadav, J. S.; Rao, A. V. R. Carbohydr. Res. 1984, 129,
267e270; (c) Edwards, O. E.; Purushothaman, K. K. Can. J. Chem. 1964, 42,
712e716; (d) Boyer, J. H.; Canter, F. C. Chem. Rev. 1954, 54, 1e57.
5. Shah, S. R.; Navathe, S. S.; Dikundwar, A. G.; Guru Row, T. N.; Vasella, A. T. Eur. J.
Org. Chem. 2013, 264e267.
6. Patonay, T.; Konya, K.; Juhasz-Toth, E. Chem. Soc. Rev. 2011, 40, 2797e2847.
ꢀ
7. (a) Verhe, R.; De Kimpe, N. Synthesis and Reactivity of a-Halogenated Ketones.
In Halides, Pseudo-Halides and Azides; Patai, S., Rappoport, Z., Eds.;
John Wiley & Sons: Chichester, UK, 1983; pp 813e931; (b) De Kimpe, N.; Verhe,
4.7.3. 1-Azido-1-(4-nitrophenyl)-1-phenylmethane (2t). Colourless
oil. Yield: 89%; Rf (10% hexane/ethylacetate) 0.47; IR (thin film):
3079, 3031, 2856, 2100, 1605, 1519, 1492, 1454, 1411, 1346, 1242,
ꢀ
ꢀ
ꢀ
1180 cmꢀ1 1H NMR (400 MHz, CDCl3): 8.11e8.15 (2H, m, ArH),
;
7.41e7.44 (2H, m, ArH), 7.26e7.34 (3H, m, ArH), 7.18e7.21 (2H, m,
ArH), 5.72 (1H, s, CH); 13C NMR (100.53 MHz, CDCl3): 147.4, 146.7,
138.2, 129.1, 128.8, 128.0, 127.5, 123.9, 67.6; HRMS (ESI): calcd for
C
13H10NO2 (MþꢀN3) m/z 212.0706. Found 212.0759.
4.7.4. 1-Azido-1,1-bis(4-fluorophenyl)methane23
(2u). Colourless
oil. Yield: 90%; Rf (5% hexane/ethylacetate) 0.64; IR (thin film):
3045, 2926, 2476, 2100, 1898, 1604, 1505, 1417, 1228, 1157 cmꢀ1; 1H
NMR (400 MHz, CDCl3): 7.17e7.20 (4H, m, ArH), 6.95e7.00 (4H, m,
ArH), 5.61 (1H, s, CH); 13C NMR (100.53 MHz, CDCl3): 162.4 (d),
135.2 (d), 129.0 (d), 115.7 (d), 67.1.
R. The Chemistry of
a-Haloketones, a-Haloaldehydes and a-Haloimines; Wiley:
Chichester, New York, Brisbane, Toronto, Singapore, 1988; (c) Smith, A. G.;
Johnson, J. S. Org. Lett. 2010, 12, 1784e1787; (d) Prakash, O.; Pannu, K.; Prakash,
R.; Batra, A. Molecules 2006, 11, 523e527; (e) Patonay, T.; Hoffman, R. V. J. Org.
Chem. 1994, 59, 2902e2905; (f) Patonay, T.; Patonay-Peli, E.; Litkei, G.; Szilagyi,
L.; Batta, G.; Dinya, Z. J. Heterocycl. Chem. 1988, 25, 343e347; (g) Creary, X.;
Rollin, A. J. J. Org. Chem. 1979, 44, 1798e1806.
8. Kumar, H. M. S.; Reddy, B. V. S.; Anjaneyulu, S.; Yadav, J. S. Tetrahedron Lett. 1998,
39, 7385e7388.
9. (a) Srinu, G.; Srihari, P. Tetrahedron Lett. 2013, 54, 2382e2385; (b) Rueping, M.;
Vila, C.; Uria, U. Org. Lett. 2012, 14, 768e771; (c) Side products are also reported
using BF3$OEt2 and AgOTf as catalyst.
4.7.5. 1-Azido-1-(4-trifluoromethylphenyl)-1-phenylmethane
(2v). Colourless oil. Yield: 88%; Rf (5% hexane/ethylacetate) 0.66; IR
(thin film): 3064, 3030, 2958, 2856, 2102, 1618, 1602, 1492, 1453,
1413, 1324, 1253, 1164, 1124, 1089, 1067 cmꢀ1 1H NMR (400 MHz,
;
CDCl3): 7.53 (2H, d, J¼8.2 Hz, ArH), 7.36 (2H, d, J¼8.2 Hz, ArH),
7.23e7.32 (3H, m, ArH), 7.20e7.22 (2H, m, ArH), 5.68 (1H, s, CH); 13
C
NMR (100.53 MHz, CDCl3): 143.5, 138.7, 129.0, 128.5, 127.6, 127.5,
125.7, 125.7, 125.6, 67.9; HRMS (ESI): calcd for C14H10F3 (MþꢀN3) m/
z 235.0729. Found 235.0727.
10. Chen, G.; Wang, Z.; Wu, J.; Ding, K. Org. Lett. 2008, 10, 4573e4576.
11. During the azidation of anisoin, there was also a second spot on the TLC plate,
but it could not be isolated, as it decomposed back to anisoin.
12. (a) The lack of nucleophilic attack of azide ion (from TMSN3) in the case of
benzoin may be due to the non-compatibility of nucleophilicity of azide ion
4. 7. 6. 1-Azido -1-(4 -methylphenyl)-1 -phenyl methane
(2w). Colourless oil. Yield: 93%; Rf (5% hexane/ethylacetate) 0.78;
IR (thin film): 3059, 3028, 2922, 2486, 2097, 1602, 1542, 1493, 1453,
1413, 1379, 1243, 1076 cmꢀ1; 1H NMR (400 MHz, CDCl3): 7.21e7.26
(5H, m, ArH), 7.06e7.20 (4H, m, ArH), 5.59 (1H, s, CH), 2.25 (3H, s,
with the electrophilicity of the less stable and short-lived a-ketocarbenium ion.
As a result, the leaving group (TMSOH) does not have the time to diffuse away.
Alternatively, the facile reaction of hydroxyl group in benzoin occurs with
TMSN3 to give trimethylsilyl-protected benzoin. (b) Appel, R.; Mayr, H. J. Am.
Chem. Soc. 2011, 133, 8240e8251 and references cited therein.

10732
A. Kumar et al. / Tetrahedron 69 (2013) 10724e10732
13. (a) 2-Hydroxy-1,2,2-triarylethanones have been prepared by reacting the ap-
propriate Grignard reagent with benzil or its derivatives using the reported
procedures. (b) Baddar, F. G.; Fahmy, F. M.; Aly, N. F. J. Indian Chem. Soc. 1973, L,
586e588; (c) Eastham, J. F.; Huffaker, J. E.; Raaen, V. F.; Collins, C. J. J. Am. Chem.
Soc. 1956, 78, 4323e4328.
16. (a) Dao, L. H.; Maleki, M.; Hopkinson, A. C.; Lee-Ruff, E. J. Am. Chem. Soc. 1986,
108, 5237e5242; (b) Creary, X. Acc. Chem. Res. 1985, 18, 3e8; (c) Creary, X.;
Geiger, C. C. J. Am. Chem. Soc. 1983, 105, 7123e7129; (d) Creary, X.; Geiger, C. C. J.
Am. Chem. Soc. 1982, 104, 4151e4162.
17. (a) Synthesis of enantioenriched 1-(4-nitrophenyl)-1-phenylmethanol (1t) was
carried out according to the reported procedure: A suspension of the [RuCl2(-
mesitylene)]2 (0.01 mmol) and ligand (1R,2R)-N-(p-toluenesulfonyl)-1,2-
diphenylethylenediamine [(R,R)-TsDPEN] (0.027 mmol) in DCM was stirred at
14. (a) In this case, the naphthyl ring, present at the carbon bearing hydroxyl
group, tends to stabilize the
extended conjugation despite the presence of eCOAr, which is an electron-
withdrawing group. As a result, the -ketocarbenium ion has enough time to
a-ketocarbenium ion more effectively due to its
a
20 ꢂC for 30 min. After removal of DCM by
a stream of N2, 4-nitro-
undergo intramolecular rearrangement to give benzofuran derivative. (b) Ku-
mar, A.; Pal, A. K.; Anand, R. D.; Singh, T. V.; Venugopalan, P. Tetrahedron 2011,
67, 8308e8313.
benzophenone (1 mmol) in a mixture of HCOOH/Et3N (5:2 mol ratio, 0.25 mL)
was added. The reaction mixture was stirred at 50 ꢂC for 2 h. After cooling to
room temperature, the reaction mixture was extracted with ethylacetate. The
sample was then dissolved in HPLC eluant (4:1) hexane/ethylacetate and ana-
lysed by HPLC for the determination of enantiomeric excess. (b) Slungard, S. V.;
Krakeli, T.-A.; Thevdt, T. H. K.; Fuglseth, E.; Sundby, E.; Hoff, B. H. Tetrahedron.
2011, 67, 5642e5650.
15. (a) The azidation of a-hydroxyketone having tert-butyl group, such as pivaloin
(4-hydroxy-2,2,5,5-tetramethylhexane-3-one) was carried out. To a solution
of pivaloin (200 mg, 1.16 mmol) and TMSN3 (200 mg, 1.74 mmol) in CH2Cl2
(5 mL) was added InBr3 (40 mg, 0.11 mmol) at room temperature. After stirring
the contents for 5 h, the reaction was quenched with water (1 mL). The re-
action mixture was extracted with CH2Cl2 (2ꢁ15 mL), washed with water and
dried over anhydrous Na2SO4. The solvent was allowed to evaporate at room
temperature to obtain a white solid. Its IR and 1H NMR were recorded. These
data showed that the starting material remained unchanged. (b) For the
preparation of pivaloin: Newman, M. S.; Arkell, A. J. Org. Chem. 1959, 24,
385e387.
18. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923e2925.
19. Shirini, F.; Mollarazi, E. Catal. Commun. 2007, 8, 1393e1396.
20. Shrini, F.; Mollarazi, E. Synth. Commun. 2006, 36, 1109e1115.
21. Chiba, S.; Zhang, L.; Ang, G. Y.; Hui, B. W.-Q. Org. Lett. 2010, 12, 2052e2055.
22. Murali, A.; Puppala, M.; Varghese, B.; Baskaran, S. Eur. J. Org. Chem. 2011,
5297e5302.
23. Alagiri, K.; Prabhu, K. R. Tetrahedron 2011, 67, 8544e8551.