Convenient and stereoselective synthesis of (Z)-1-bromo-1-alkenes by microwave-induced reaction

Article abstract of DOI:10.1016/S0040-4039(01)00595-0

(Z)-1-Bromo-1-alkenes were stereoselectively prepared in high yields in a short reaction time (0.2-1.0 min) by microwave irradiation of the corresponding 2,3-dibromoalkanoic acids in DMF in the presence of triethylamine.

Full text of DOI:10.1016/S0040-4039(01)00595-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3893–3896
Convenient and stereoselective synthesis of
(Z)-1-bromo-1-alkenes by microwave-induced reaction
Chunxiang Kuang, Hisanori Senboku and Masao Tokuda*
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Received 19 February 2001; revised 26 March 2001; accepted 6 April 2001
Abstract—(Z)-1-Bromo-1-alkenes were stereoselectively prepared in high yields in a short reaction time (0.2–1.0 min) by
microwave irradiation of the corresponding 2,3-dibromoalkanoic acids in DMF in the presence of triethylamine. © 2001 Elsevier
Science Ltd. All rights reserved.
(Z)-1-Bromo-1-alkenes are an important synthetic
intermediate for stereospecific synthesis of substituted
alkenes. A variety of methods have been reported for
the stereocontrolled preparation of (Z)-1-bromo-1-alke-
nes, including Wittig-type reaction,1 metal–halogen
exchange of metalloalkenes,2 hydroboration–protonoly-
sis of haloalkynes,3 palladium-catalyzed hydrogenolysis
of 1,1-dibromo-1-alkenes by tributyltin hydride,4 reduc-
tion of 1-haloalkynes with diimine,5 transformation of
ketones using an appropriate acetyl halide in a strongly
acidic solvent,6 SmI2-mediated b-elimination of O-ace-
tyl dihalo alcohols,7 and debrominative decarboxyla-
tion of cinnamic and acrylic acid dibromides.8
Debrominative decarboxylation of brominated a,b-
unsaturated carboxylic acids8 might be one of the most
useful methods for a synthesis of (Z)-1-bromo-1-alke-
nes since the starting a,b-unsaturated acids are readily
available and the procedure is very simple. However,
the yields are low in the case of aliphatic (Z)-1-bro-
moalkenes and (Z)-b-bromostyrene carrying ortho- and
para-nitro-substituents even if an improved procedure
using triethylamine and DMF solvent was used in these
reactions.8i Recently, we found that microwave irradia-
tion in the reported improved procedure resulted in
highly selective formation of (Z)-1-bromo-1-alkenes
with excellent yields. In this communication, we report
a convenient method for an efficient and stereoselective
synthesis of (Z)-1-bromo-1-alkenes by microwave irra-
diation of 2,3-dibromoalkanoic acids with a short reac-
tion time.
Microwave-induced rate acceleration technology is
becoming a powerful tool in organic synthesis.9 We also
reported a microwave-induced reaction for a stereose-
lective synthesis of (E)-b-arylvinyl halides from a,b-
unsaturated carboxylic acids.10 Therefore, we can
successfully achieve a highly stereoselective synthesis of
both (E)- and (Z)-vinyl bromides, starting from the
same a,b-unsaturated carboxylic acids, by using a
microwave irradiation technique.
2,3-Dibromoalkanoic acids (2) were readily obtained by
bromination of the corresponding trans-a,b-unsatu-
rated carboxylic acids ((E)-1) in CHCl3 at rt to 60°C or
by bromination of (E)-1 in CHCl3 under irradiation
with a tungsten lump. Microwave irradiation of anti-
2,3-dibromoalkanoic acids (2), in DMF solution con-
taining 1.05 equiv. of triethylamine for 0.2–1.0 min,
Br
Et3N / DMF
Br2
R
CO2H
CO2H
R
R
Br
CHCl3
Br
MW, 0.2-1.0 min
(E)-1
2
(Z)-3
Scheme 1.
Keywords: (Z)-vinyl bromide; a,b-unsaturated carboxylic acids; decarboxylation; microwave irradiation.
* Corresponding author. Fax: +81-11-706-6598; e-mail: tokuda@org-mc.eng.hokudai.ac.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00595-0

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C. Kuang et al. / Tetrahedron Letters 42 (2001) 3893–3896
gave the corresponding (Z)-vinyl bromides ((Z)-3) in
excellent yields and high (Z)-selectivities (Scheme 1).
The yields of (Z)-3 and the ratios of (Z) and (E) are
summarized in Table 1.
Table 1. Stereoselective synthesis of (Z)-vinyl bromides (3) by microwave irradiation of 2,3-dibromoalkanoic acids (2)
Entry
1
Product (3)
R of 2
MW (min)
0.5
Yield of 3 (%)a)
Z /E b)
C6H5
>99 / 1
95
Br
4-CH3C6H4
98
98 / 2
2
0.5
Br
Me
4-CH3OC6H4
3,4-OCH2OC6H3
4-ClC6H4
0.5
0.5
1.0
75 / 25
95 / 5
3
4
5
95
99
96
Br
MeO
O
Br
O
>99.5 / 0.5
Cl
Br
Br
2-ClC6H4
1.0
1.0
94
98
98 / 2
6
7
4-NO2C6H4
>99.5 / 0.5
3-NO2C6H4
2-NO2C6H4
8
9
1.0
1.0
99
96
99
>99.9 / 0.1
>99.5 / 0.5
>99.9 / 0.1
O2N
4-CH3O2CC6H4
2-Naphthyl
3-Pyridyl
10
11
12
1.0
0.5
1.0
Br
MeO2C
96
73
>99.5 / 0.5
>99.9 / 0.1
Br
Br
N
n-C7H15
n-C7H15
c-C6H11
0.2
0.2
91
82
13
14
>99.9 / 0.1
>99.9 / 0.1
Br
Br
a) Isolated yields.
b) Determined by 1H NMR.
Br
R
Et3N / DMF
MW, 5 s
Br2
HBr / AcOH
CO2H
Br
R
R
CO2H
(Z)-1
Br
(E)-3
4
[ R= C6H5: 95%, E /Z = 99 / 1 ]
Scheme 2.

C. Kuang et al. / Tetrahedron Letters 42 (2001) 3893–3896
3895
bon dioxide and bromide ion to give (Z)-vinyl bro-
mides (Scheme 3). On the other hand, in the case of
3-p-anisyl-2,3-dibromopropanoic acid, a unimolecular
elimination process of bromide ion to give relatively
stable carbocations A and B may be involved. Elimina-
tion of carbon dioxide from A and B would give (Z)-
and (E)-vinyl bromide, respectively, with a preferential
formation of (Z)-isomer (Scheme 4).
These results indicate that the present microwave-
induced reaction can be used for the synthesis of both
aromatic and aliphatic (Z)-1-bromo-1-alkenes. Cin-
namic acid dibromides carrying electron-donating or
electron-withdrawing groups could be converted into
the corresponding (Z)-b-bromostyrenes in excellent
yields with high stereoselectivities (entries 2–10). It is
noteworthy that the yields of (Z)-b-bromostyrenes car-
rying nitro groups (entries 7–9) and those of aliphatic
(Z)-1-bromo-1-alkenes (entries 13 and 14) increased to
82–98%, although even an improved method of
debrominative decarboxylation in DMF at 80°C gave
those vinyl bromides in 41–61% yield.8i The stereoselec-
tivity of Z/E was lowered to 75% only in the case of
p-methoxyphenyl vinyl bromide (entry 3). However, all
of the results in Table 1 indicate that the yields and
Z/E stereoselectivities by the present method are quite
higher than those of previous procedures.8i,8j
The typical experimental procedure is as follows: A
mixture of cinnamic acid dibromide (1 mmol) and
triethylamine (1.05 mmol) was added to 2 ml of DMF.
The mixture was kept inside a microwave oven oper-
ated at 2450 MHz (Toshiba, ER-V11, 200 W) and was
irradiated for 0.5 min without any stirring. The reaction
mixture was then removed from the oven and cooled to
room temperature. Water and ether were added to the
reaction mixture and the organic layer was separated.
The aqueous layer was extracted with ether. The com-
bined organic layers were washed with water and brine,
and dried over anhydrous magnesium sulfate. Evapora-
tion of the solvent gave almost pure (Z)-b-bro-
mostyrene in 95% yield (Z/E >99/1). Large scale
reaction using 20 mmol of cinnamic acid dibromide
also proceeded in the same way to give (Z)-b-bro-
mostyrene in 95% yield (Z/E >99/1).
The present microwave-induced method can be applied
to a synthesis of (E)-vinyl bromides. Microwave irradi-
ation of syn-2,3-dibromoalkanoic acids (4), prepared by
bromination of cis-a,b-unsaturated acids ((Z)-1),11 for
5 s under the same conditions as those for 2 furnished
(E)-vinyl bromide ((E)-3) stereoselectively in 95% yield
(Scheme 2). These results show that the present
debrominative decarboxylation by microwave irradia-
tion proceeds in a highly stereospecific manner from
either anti- or syn-2,3-dibromoalkanoic acid.
In conclusion, we have developed a rapid and conve-
nient method for an efficient and stereoselective synthe-
sis of (Z)-1-bromo-1-alkenes from the corresponding
2,3-dibromoalkanoic acids using a triethylamine/DMF
system under microwave irradiation. The present
debrominative decarboxylation of dibrominated cin-
namic and acrylic acids using microwave irradiation
was found to have significant advantages over existing
procedures.
Two proposed reaction pathways for the present
debrominative decarboxylations are shown in Schemes
3 and 4. Most of the reactions probably proceed via
trans-b-elimination involving simultaneous loss of car-
O-
O
H
H
R
Br
Acknowledgements
Et3N
DMF
CO2H
R
R
Br
(Z)-3
Br
This work was supported by a Grant-in-Aid for Scien-
tific Research on Priority Areas (No. 706: Dynamic
Control of Stereochemistry) from the Ministry of Edu-
cation, Science, Sports and Culture, Japan.
Br
2
Br
Scheme 3.
O
O
Br
CO2H
H
O
An
Et3N
DMF
O
H
+
H
H
H
An
H
An
Br
Br
Br
B
A
( An = p-CH3OC6H4 )
An
Br
An
Br
(Z)-3
(E)-3
Scheme 4.

3896
C. Kuang et al. / Tetrahedron Letters 42 (2001) 3893–3896
quemiller, R.; Figade`re, B. Tetrahedron Lett. 1999, 40,
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