Tetrahedron Letters
Metal-free regioselective hydrobromination of alkynes through CAH/
CABr activation
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Xiuling Chen, Tieqiao Chen, Yuqiang Xiang, Yongbo Zhou , Daoqing Han, Li-Biao Han, Shuang-Feng Yin
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A metal-free regioselective hydrobromination of alkynes has been developed to provide the Markovni-
kov-type vinyl bromides in good yields using dibromomethane/N,N-dimethylaniline as in-situ ‘HBr’
source. This protocol also represents an elegant example of the activation of sp2 CAH and CABr bonds
in one pot, in which ‘HBr’ is generated and transferred under mild metal-free conditions. D-incorporated
experiments were employed to investigate the reaction mechanism and a plausible reaction path was
proposed.
Received 10 April 2014
Revised 9 June 2014
Accepted 17 June 2014
Available online xxxx
Keywords:
Hydrobromination
Alkynes
Ó 2014 Elsevier Ltd. All rights reserved.
Dibromomethane
Markovnikov-type adducts
Introduction
Herein, we report a novel alternative procedure for the synthe-
sis of vinyl bromides employing CH2Br2/N,N-dimethylaniline as in-
Vinyl bromides play an important role in organic synthesis. They
often emerge as versatile substrates in a variety of chemical trans-
formations.1–4 Conventional procedures for the preparation of these
compounds depend on the addition of HBr gas to alkynes, however,
the direct use of toxic and corrosive HBr gas hinders their applica-
tions in synthetic processes.5 To avoid experimental hazard, many
efforts have been made to develop in-situ ‘HBr’ systems in place of
HBr gas for the synthesis of vinyl bromides using non- or low toxic-
ity/causticity and easily-handled liquids or solids.6–9 In the year
2003, Weiss reported an efficient system for the hydrobromination
of alkynes using quaternary ammonium bromide and trifluoroacetic
acid.6 Subsequently, Thongsornkleeb and co-workers utilized LiBr-
TMSCl-TEAB to prepare vinyl bromides.7 The notable recent
advancement was achieved by Hoveyda and co-workers, they devel-
oped a Ni-catalyzed hydrobromination of alkynes using N-bromo-
succinimide and diisobutylaluminum hydride as in-situ ‘HBr’
source, which was smoothly performed to produce vinyl bromides
situ ‘HBr’ source (Eq. 1). This protocol also represents an elegant
example of combining successfully CAH bond activation, CABr
bond cleavage, and hydrobromination of alkynes, in which the
in-situ ‘HBr’ is generated and transferred under metal-free condi-
tions. To the best of our knowledge, there is no precedent for
CAH bond and CABr bond cleavage under metal-free conditions
to synthesize vinyl bromides.
Results and discussion
During studies on the three-component coupling reaction of
phenylacetylene, dichloromethane, and N,N-dimethylaniline to
produce propargylamines,10 we accidentally found the formation
of (1-bromovinyl)benzene 2a via hydrobromination of alkynes
using CH2Br2 instead of CH2Cl2 in the absence of silver catalyst.
For example, under N2 atmosphere, 0.5 mmol of phenylacetylene
reacted with 0.5 mmol of N,N-dimethylaniline and 0.5 mmol
CH2Br2 at 120 °C for 12 h, the product (1-bromovinyl)benzene 2a
was produced in 10% yield (Table 1, entry 1). To improve the yield,
amounts of N,N-dimethylaniline and CH2Br2 were screened (Table 1,
entries 2–4). When 0.5 mmol of phenylacetylene, 1.5 mmol of N,N-
dimethylaniline, and 2.5 mmol of CH2Br2 were loaded, the yield and
regioselectivity increased to 91% and 92%, respectively. Interest-
ingly, under air atmosphere, the reaction also gave similar results,
indicating that air did not affect the reaction (Table 1, entry 5). Fur-
ther control experiments showed that this hydrobromination was
sensitive to temperature. For example, under similar conditions,
in high yields with high a
-selectivity (95% to >98%).8 Despite those
advances, highly selective and metal-free synthetic methods to give
2-bromo-1-alkenes of great synthetic importance are still desirable.
Br
CH2Br2, N,N-dimethylaniline
R
R
ð1Þ
1
2
R = aryl or alkyl group
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Corresponding authors. Tel./fax: +86 731 88821171.
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.