LETTER
2309
A Remarkably Simple One-Step Procedure for the Preparation of
a-Bromo-a,b-Unsaturated Carbonyl Compounds
a,b
SimplePrepar tionofa-Bromo-a,b-UnsaturatedCarbonylCompounJyothi,
Divya
ds
S. HariPrasad*a
a
Abstract: An easy and convenient one-step procedure for the conversion of a,b-unsaturated carbonyl compounds into their corresponding bromo-enones using NBS–Et3N·3HBr in the presence of
potassium carbonate in dichloromethane at 0 °C to room temperature under very mild conditions in high yields and significantly
shorter times, is reported.
Key words: NBS–Et3N·3HBr, a-bromo-a,b-unsaturated carbonyl
compounds, bromination, mild conditions
a-Bromo-a,b-unsaturated carbonyl compounds form an
important class of compounds in synthetic organic chemistry. Their versatility lies in both the synthesis of a-substituted enones1 and in their ability to serve as a-ketovinyl
anion equivalents.2 These class of compounds are potential starting materials for the synthesis of natural products
and some of the bromo-enones are themselves also obtained in nature.3 They are employed in the construction
of a wide variety of biologically and medicinally important products,4 and there is a wealth of literature available
to mark its importance in natural product chemistry. To
name a few, this type of compound has been used in the
synthesis of the carbon framework of the guanacastepene
family of natural products,5 in the synthesis of taxane
diterpenes,6a in dihydrojasmones,6b and in the synthesis of
pentenomycins I-III.7 Although the preparation of these
compounds is well documented in the literature, a simpler,
milder and better alternative will always be advantageous
to the synthetic chemist.
a-Bromo-a,b-unsaturated carbonyl compounds can be
prepared by various methods. The most common being
one-pot bromination–dehydrobromination employing
bases such as triethylamine,8 pyridine,9 or sodium bicarbonate.10 Other brominating agents used are: phenylselenium bromide,11 pyridinium bromide per bromide,12
sodium bromide–Oxone,13a dimethyldioxirane and metal
halides/amberlyst 1513b or dimethylbromosulfonium bromide.14 Alternatively, conversion into the silylenol ethers
and subsequently into 1,1-dibromo-2-silyloxycyclopropane followed by elimination to form halomethylsilane
has been described.15
SYNLETT 2009, No. 14, pp 2309–2311xx. 209
Advanced online publication: 03.08.2009
DOI: 10.1055/s-0029-1217726; Art ID: D06409ST
© Georg Thieme Verlag Stuttgart · New York
The reported methods can entail low yields, difficulty in
handling hazardous bromine as well as maintaining its
stoichiometric ratio, expensive reagents, longer reaction
times, multiple steps, cumbersome product isolation and
environmental pollution. Moreover, the replacement of
toxic organic reagents is one of the important goals in
green chemistry.16
In a continuation of our studies on the synthesis and reactions of some novel cyclic vinyl silanes,17 we needed supplies of a-bromo-a,b-unsaturated carbonyl compounds,
which could be used as starting materials for the preparation of olefinic organosilicon compounds.
Direct access to a-bromo-methylcyclohexenone (2a) by
the usual protocol of bromination–dehydrobromination
was not feasible even under different conditions and solvents because of its marked tendency to aromatize even
under the mildest alkaline conditions.18 In our efforts to
identify an efficient approach, we found two useful methods involving the use of DMP19 and TBATB.20 However,
the expensive reagents, availability, time duration, scalability and isolation methods were problematic. So designing a simple and efficient method for the preparation
of the starting material was necessary.
Among other brominating agents, N-bromosuccinimide
(NBS) should be considered the reagent of first choice because of its ready availability and ease of handling.
Heasley21 illustrated the effect of NBS on the bromination
of a,b-unsaturated ketones, and isolated significantly lower amounts of the dibromides. This prompted us to choose
a suitable brominating agent that can enhance the efficiency of the dibromide formation. Due to the potential of
NBS–Et3N·HBr as a brominating agent, we expected to
form a-bromo-a,b-unsaturated carbonyl compounds upon
bromination of ketones with the above reagent. Thus, the
procedure22 developed in this study involves the reaction
of a,b-unsaturated ketones with NBS–Et3N·3HBr in anhydrous dichloromethane at 0 °C, followed by treatment
with potassium carbonate and stirring at room temperature to give the bromo-ketones in very high yields. Surprisingly when we extended the same method to
substrates 1g, 1h and 1i (Table 1), we could isolate the desired products in good yields after simple workup and
chromatographic purification.
In conclusion, we describe in this paper, a versatile, simple and environmentally friendly one-step procedure for
the conversion of a,b-unsaturated ketones into their corre-
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Department of Studies in Chemistry, Central College Campus, Bangalore University, Bangalore 560001, India
E-mail: hariprasad@bub.ernet.in
b
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Received 2 March 2009
LETTER
D. Jyothi, S. HariPrasad
sponding bromo-enones. The very mild method uses
NBS–Et3N·3HBr in the presence of potassium carbonate
in anhydrous dichloromethane at 0 °C to room temperature, and gives high yields in short reaction times.
Table 1 a-Bromination of a,b-Unsaturated Carbonyl Compounds
using NBS–Et3N·3HBr
Entry
Substrate
Time (min) Producta
O
Yield (%)b
O
a
Br
25
1a
88
2a
O
O
b
Br
22
1b
83
2b
O
O
c
24
1c
Br
86
Br
89
2c
O
O
d
24
1d
2d
O
O
Br
e
32
1e
89
2e
O
O
Br
f
28
1f
81
2f
O
g
O
Br
30
O
O
1g
2g
O
HN
h
O
O
N
H
O
76
N
H
O
2h
O
O
i
Br
HN
35
1h
Me
78
Me
N
30
N
O
76
N
Me
Me
1i
Br
N
2i
a
The products were characterized by melting points, IR, 1H NMR,
and 13C NMR spectroscopy, and mass spectrometry.
b
Isolated yield.
Synlett 2009, No. 14, 2309–2311
© Thieme Stuttgart · New York
Acknowledgment
We are thankful to the Organic Chemistry and NMR departments,
Indian Institute of Science, Bangalore. Grateful thanks are due to
the University Grants Commission and the Department of Science
and Technology, New Delhi, India for finacial assistance.
References and Notes
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2310
Simple Preparation of a-Bromo-a,b-Unsaturated Carbonyl Compounds
B.; Shibuya, T. Y.; Stanley, M. S.; Shellhamer, D. F.;
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(22) Typical Procedure: To a stirred solution of 3-methylcyclohex-2-en-1-one (1a; 2.5 g, 13.23 mmol) in anhydrous
CH2Cl2 (25 mL) were added NBS (14 mmol), Et3N·3HBr
(23 mmol) and K2CO3 (40 mmol) at 0 °C. After 10 min the
reaction mixture was slowly brought to r.t. and stirring was
continued. The reaction was complete within 25 min as
monitored by GC [SE-30 SS; 2m × 1/8¢¢ column on
Shimadzu 14-B/Mayura 9800 gas chromatographs]. The
residual solid was filtered off and the solid residue was
washed with anhydrous CH2Cl2 (15 mL). The combined
filtrate was concentrated under vacuum and the crude
2311
product was purified by chromatography (silica gel; EtOAc–
hexane, 1:4) to afford, after concentration, the product 2a as
light-yellow oil in 88% yield. IR (neat): 2920 (S), 1695 (S),
1605 (S), 1255 (S). 1H NMR (400 MHz, CDCl3): d = 2.59 (t,
J = 6.7 Hz, 2 H), 2.52 (t, J = 6 Hz, 2 H), 2.18 (s, 3 H), 2.05–
1.97 (m, 2 H). 13C NMR (400 MHz, CDCl3): d = 190.9
(C=O), 160.3 (C), 122.7 (CH), 37.6 (CH2), 25.9 (CH3), 21.8
(CH2). GCMS (Shimadzu GC-17A coupled to Shimadzu
GC-MS QP 5050 A with capillary column: BP 5, length: 30 m):
m/z (%) = 190 (10), 188 (15), 162 (25), 160 (30), 132 (5), 127
(7), 190 (12), 93 (4), 83 (4), 81 (30), 79 (25), 76 (5), 66 (10),
52 (10), 67 (8), 63 (19), 56 (5), 55 (13), 53 (80), 51 (47), 50
(32), 43 (13), 42 (100), 41 (88), 40 (60).
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LETTER
Synlett 2009, No. 14, 2309–2311
© Thieme Stuttgart · New York