Tetrahedron Letters
Facile generation of a,a-dibromodimethyl ketals
from alkynes using TsNBr2
⇑
Kamal Krishna Rajbongshi, Prodeep Phukan
Department of Chemistry, Gauhati University, Guwahati 781014, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
TsNBr2 reacts with alkyne in the presence of methanol to form
a,a-dibromodimethyl ketals instanta-
Received 28 December 2013
Revised 24 January 2014
Accepted 25 January 2014
Available online 1 February 2014
neously. The reaction proceeds smoothly at room temperature without using any other catalyst. The
one step reaction can be carried out with both aromatic and aliphatic alkynes in excellent yield.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
TsNBr2
Alkyne
Dibromodimethyl ketal
Methanol
Activation and functionalization of carbon–carbon triple bond is
an important strategy for many important organic transformations
in synthetic chemistry.1 One of the common strategies used for
functionalization of carbon–carbon multiple bond is the cohalo-
genation reaction. This reaction is an attractive tool to produce vic-
inal halo-functionalized compounds regioselectively, which are
useful intermediates for diverse organic transformations.2
Although cohalogenation reaction for C–C double bond is exten-
sively studied, this protocol is less common for C–C triple bond.
Recently, we have established that N,N-dibromo-p-toluenesul-
fonamide (TsNBr2) is a very efficient and powerful reagent for var-
ious organic transformations.3 We found that TsNBr2 can be used
as an electrophilic bromine source for vicinal bromo functionaliza-
tion of olefin and we have successfully employed this reagent for
various cohalogenation reactions.3a,b,f Based on this concept, we in-
tended to investigate the reaction of alkyne with TsNBr2 in the
presence of nucleophilic solvent such as methanol. Interestingly,
They carried out the reaction at 20 °C under the influence of ultra-
sonic irradiation as well as at room temperature with continuous
stirring. Similar to Uemura’s report, this procedure also leads to
the formation of E-
a,b-dibromoalkene as the side product in signif-
icant amount. Bovonsombat and McNelis reported the synthesis of
some ketals of
a,a-dihaloacetophenone using N-halosuccinimide
and catalytic quantity of p-toluenesulfonic acid.6 Heasley and co-
workers reported a procedure for the synthesis of dihalo acetals
from alkyne using NBS or NIS as the halogen source.7 In this case,
H2SO4 was used as a catalyst to achieve the transformation. Samuel
reported another method for the synthesis of a,a-dichlorodimethyl
ketals from acetylene using NCS in methanol.8 However, most of
the reported methods have some limitations such as the use of cat-
alyst, low yield, and formation of byproducts which make the pro-
cedures inconvenient for preparations. We wish to report herein a
very simple and efficient method for direct synthesis of
a,a-dib-
romodimethyl ketals from alkyne using N,N-dibromo-p-toluene-
sulfonamide (TsNBr2) as a bromine source under mild conditions
(Scheme 1).
to our expectation,
a
,a-dibromodimethyl ketal was formed in
excellent yield. However, the synthesis of
a,a
-dibromodimethyl
ketal has received scant attention in the literature, with only a
few methods outlined. Uemura found that the treatment of acety-
lenes with bromine in methanol at 20–25 °C leads to the formation
To begin with, a study was carried out with phenyl acetylene as
a model substrate. A reaction was carried out by adding TsNBr2
(1 mmol) to a solution of phenyl acetylene (1 mmol) in the
of
a,a
-dibromodimethyl ketals in moderate yield.4 The reaction
also produces an isomeric mixture of
a
,b-dibromoalkenes along
H3CO OCH3
with the desired product. Similar attempt was also made by Berth-
TsNBr2
2
1
1
2
elot et al. with tetrabutylammonium tribromide in methanol.5
R
Br
R
R
R
MeOH,rt
Br
Instantaneous
2
1
⇑
Corresponding author. Tel.: +91 361 2570535; fax: +91 361 2700311.
Scheme 1. Synthesis of a,a-dibromodimethyl ketal.
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.