A remarkably simple one-step procedure for the preparation of α-bromo-α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1055/s-0029-1217726

An easy and convenient one-step procedure for the conversion of α,β-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. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217726

LETTER
2309
A Remarkably Simple One-Step Procedure for the Preparation of
a-Bromo-a,b-Unsaturated Carbonyl Compounds
S
a
imple Preparation
i
of
a
-B
v
romo-
a
,
b
-U
y
nsaturated
C
a
a
rbonyl Compoun
J
ds yothi,a,b S. HariPrasad*a
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
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
Abstract: An easy and convenient one-step procedure for the con-
version of a,b-unsaturated carbonyl compounds into their corre-
sponding bromo-enones using NBS–Et3N·3HBr in the presence of
potassium carbonate in dichloromethane at 0 °C to room tempera-
ture under very mild conditions in high yields and significantly environmental pollution. Moreover, the replacement of
shorter times, is reported.
toxic organic reagents is one of the important goals in
green chemistry.16
Key words: NBS–Et3N·3HBr, a-bromo-a,b-unsaturated carbonyl
compounds, bromination, mild conditions
In a continuation of our studies on the synthesis and reac-
tions of some novel cyclic vinyl silanes,17 we needed sup-
plies of a-bromo-a,b-unsaturated carbonyl compounds,
a-Bromo-a,b-unsaturated carbonyl compounds form an
important class of compounds in synthetic organic chem-
istry. Their versatility lies in both the synthesis of a-sub-
stituted enones1 and in their ability to serve as a-ketovinyl
anion equivalents.2 These class of compounds are poten-
tial starting materials for the synthesis of natural products
and some of the bromo-enones are themselves also ob-
tained in nature.3 They are employed in the construction
of a wide variety of biologically and medicinally impor-
tant 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.
which could be used as starting materials for the prepara-
tion 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 sol-
vents 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 meth-
ods involving the use of DMP19 and TBATB.20 However,
the expensive reagents, availability, time duration, scal-
ability and isolation methods were problematic. So de-
signing 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 be-
cause 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 low-
er amounts of the dibromides. This prompted us to choose
a suitable brominating agent that can enhance the efficien-
cy 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 an-
hydrous dichloromethane at 0 °C, followed by treatment
with potassium carbonate and stirring at room tempera-
ture to give the bromo-ketones in very high yields. Sur-
prisingly when we extended the same method to
substrates 1g, 1h and 1i (Table 1), we could isolate the de-
sired products in good yields after simple workup and
chromatographic purification.
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 bicar-
bonate.10 Other brominating agents used are: phenylsele-
nium bromide,11 pyridinium bromide per bromide,12
sodium bromide–Oxone,13a dimethyldioxirane and metal
halides/amberlyst 1513b or dimethylbromosulfonium bro-
mide.14 Alternatively, conversion into the silylenol ethers
and subsequently into 1,1-dibromo-2-silyloxycyclopro-
pane followed by elimination to form halomethylsilane
has been described.15
In conclusion, we describe in this paper, a versatile, sim-
ple and environmentally friendly one-step procedure for
the conversion of a,b-unsaturated ketones into their corre-
SYNLETT 2009, No. 14, pp 2309–2311
Advanced online publication: 03.08.2009
DOI: 10.1055/s-0029-1217726; Art ID: D06409ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.x
x
.2
0
0
9

2310
D. Jyothi, S. HariPrasad
LETTER
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 tempera-
ture, and gives high yields in short reaction times.
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.
Table 1 a-Bromination of a,b-Unsaturated Carbonyl Compounds
using NBS–Et3N·3HBr
References and Notes
Entry
a
Substrate
Time (min) Producta
Yield (%)b
88
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Br
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25
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2a
O
O
b
22
83
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2b
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Br
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c
24
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86
89
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O
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d
1d
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2d
2e
O
Br
e
32
89
1e
O
O
Br
f
28
30
35
81
78
76
1f
2f
O
O
O
Br
g
h
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1g
2g
O
O
Br
HN
HN
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O
N
H
O
N
H
1h
2h
Me
O
O
O
Br
Me
O
N
N
i
30
76
N
N
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Me
Me
1i
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

LETTER
Simple Preparation of a-Bromo-a,b-Unsaturated Carbonyl Compounds
2311
B.; Shibuya, T. Y.; Stanley, M. S.; Shellhamer, D. F.;
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).
Heasley, G. E. J. Org. Chem. 1988, 53, 2199.
(22) Typical Procedure: To a stirred solution of 3-methylcyclo-
hex-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
Synlett 2009, No. 14, 2309–2311 © Thieme Stuttgart · New York