1752
LETTER
Stereoselective Synthesis of (Z)-b-Chlorovinyl Sulfones by Addition of Sulfonyl
Chlorides to Acetylenes
Stereoselective
Sy
u
nthesis of
(
Z
e
b
-Chlorov
y
inyl Sulfone
u
s
an Liu,a Xinhua Duan,a Zhenliang Pan,a Yao Han,a Yongmin Liang*a,b
a
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China
b
State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000,
P. R. China
Fax +86(931)8912582; E-mail: liangym@lzu.edu.cn
Received 11 May 2005
CuCl is employed as the catalyst, the optimal reaction
conditions thus far achieved utilize one equivalent of
phenylacetylene, 1.5 equivalents of the sulfonyl chloride,
one equivalent of Me2S, and 10 mol% CuCl in toluene at
110 °C for four hours.9 Using the method, only (Z)-b-
chlorovinyl sulfone was accessible in an isolated yield of
87% (Table 1, entry 1), whose configuration was identi-
fied by comparisons with authoritative data.6b No E iso-
mer was detected as evidenced by the 1H NMR spectrum
of the crude reaction mixture. As can be seen in Table 1,
the key to the success of the reaction lies in the use of
Me2S. Lowering the amount of Me2S to 0.2 equivalents
resulted in lower yields (Table 1, entry 2). Control ex-
periments indicated that, in the absence of Me2S, only a
trace amount of product was observed (Table 1, entry 3).
CuCl·Me2S (10 mol%)10 was less efficient in this reaction
(Table 1, entry 4). A mixture of products were obtained
under the same conditions when CuBr or CuI was em-
ployed as the catalyst (Table 1, entries 5 and 6). The effect
of solvent is another important factor. In addition to tolu-
ene, dioxane was also effective, affording the product in
64% yield (Table 1, entry 7). Other solvents such as THF
and MeCN resulted in mixtures of products (Table 1,
entries 8 and 9). No reaction occurred in CH2Cl2 and DMF
(Table 1, entries 10 and 11).
Abstract: The addition reaction of sulfonyl chlorides with acetyl-
enes in the presence of a copper salt is described. The reaction pro-
ceeds in toluene in the presence of CuCl with Me2S as the additive
to afford only (Z)-b-chlorovinyl sulfones in moderate to excellent
yields.
Key words: halovinyl sulfones, sulfonyl chlorides, acetylenes,
CuCl/Me2S
Vinyl sulfones are extensively used as intermediates in
organic synthesis due to the chemical versatility of the
sulfone moiety.1 They are also excellent acceptors in
Michael additions,2 2p partners in cycloaddition reac-
tions,3 and intermediates of biologically active sulfone
molecules which have been found to have anticancer4 and
carcinogenesis-suppressing activity.5
Halovinyl sulfones, as an alkenylic intermediate with two
functionalities containing sulfur and chlorine, may be uti-
lized for the stereoselective synthesis of polysubstituted
alkenes. General synthetic methods to halovinyl sulfones
have been developed by the addition of sulfonyl halide to
acetylenes. However, these approaches provide either an
E/Z mixture6 or only the E isomer.7 Efficient and highly
stereoselective methodologies for the synthesis of (Z)-b-
chlorovinyl sulfones has been scarcely reported. Recent-
ly, a method for the synthesis of the Z isomer, via two
steps from acetylenic sulfones, Cp2Zr(H)Cl and various
electrophiles (NCS, NBS, I2, etc.), was reported.8 In this
paper, we wish to report a method for the stereoselective
synthesis of (Z)-b-chlorovinyl sulfones by a copper-cata-
lyzed addition of sulfonyl chlorides to acetylenes
(Scheme 1).
With these encouraging results in hand we were interested
in the scope of our new protocol. We first chose to ex-
amine the addition of phenylacetylene to a variety of
sulfonyl chlorides under standard conditions (Table 2).
Aryl sulfonyl chlorides such as p-toluenesulfonyl chloride
(1a), benzenesulfonyl chloride (1b), and 4-methoxyphe-
nylsulfonyl chloride (1c) reacted with phenylacetylene 2a
affording the corresponding products in excellent yields
(Table 2, entries 1–3). However, alkyl sulfonyl chlorides
like methanesulfonyl chloride (1d) afforded the expected
b-chlorovinyl sulfones 3d in just 52% yield after 12 hours
(Table 2, entry 4). We then chose to examine the addition
of benzenesulfonyl chloride (1b) to a variety of acetyl-
enes. The standard protocol worked well for a variety of
substituted phenylacetylenes, whether electron-rich
(Table 2, entry 5), electron-poor (Table 2, entries 6–9), or
sterically hindered (Table 2, entry 10), all of them afford-
ed good yields of product. In the case of 4-ethynylaceto-
phenone (2e) and methyl 4-ethynylbenzoate (2f), two
equivalents of benzenesulfonyl chloride was required
(Table 2, entries 8 and 9). 1-Cyclohexeneacetylene (2h)
10 mol% CuCl
Ph
Cl
H
Me2S (1.0equiv)
+
Ph
TsCl
toluene, 110 °C
Ts
Scheme 1
To optimize the reaction protocol we chose the addition of
phenylacetylene to p-toluenesulfonyl chloride as the test
reaction. The results are summarized in Table 1. When
SYNLETT 2005, No. 11, pp 1752–1754
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7
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7
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Advanced online publication: 09.06.2005
DOI: 10.1055/s-2005-869876; Art ID: U07005ST
© Georg Thieme Verlag Stuttgart · New York
Liu, Xueyuan
