Synthesis of vinyl sulfides by copper-catalyzed decarboxylative C-S cross-coupling

Article abstract of DOI:10.1021/ol101729k

A novel method for the synthesis of vinyl sulfides by the decarboxylative cross-coupling of arylpropiolic acids with thiols using copper(I) salts as catalysts has been developed. In the presence of CuI and Cs₂CO ₃, a variety of thiols reacted with arylpropiolic acids to afford the corresponding vinyl sulfides in good to excellent yields with high stereoselectivity for Z-isomers.

Full text of DOI:10.1021/ol101729k

ORGANIC
LETTERS
2010
Vol. 12, No. 18
4134-4136
Synthesis of Vinyl Sulfides by
Copper-Catalyzed Decarboxylative C-S
Cross-Coupling
Sadananda Ranjit,† Zhongyu Duan,‡ Pengfei Zhang,§ and Xiaogang Liu*,†
Department of Chemistry, National UniVersity of Singapore, 3 Science DriVe 3,
Singapore 117543, School of Chemical Engineering, Hebei UniVersity of Technology,
Tianjin 300130, China, and College of Material, Chemistry and Chemical Engineering,
Hangzhou Normal UniVersity, Hangzhou 310036, China
chmlx@nus.edu.sg
Received July 24, 2010
ABSTRACT
A novel method for the synthesis of vinyl sulfides by the decarboxylative cross-coupling of arylpropiolic acids with thiols using copper(I) salts
as catalysts has been developed. In the presence of CuI and Cs2CO3, a variety of thiols reacted with arylpropiolic acids to afford the corresponding
vinyl sulfides in good to excellent yields with high stereoselectivity for Z-isomers.
The utility of vinyl sulfides has increased enormously over
the past several years. Vinyl sulfides can be used as
complementary building blocks to carbonyl compounds1 and
Michael acceptors2 for synthesis of many polymeric materi-
als,3 natural products,4 and synthetic reagents.5 Conventional
approaches to the synthesis of vinyl sulfides include the
addition of thiols to alkynes under free-radical6 or metal-
catalyzed conditions,7 Wittig olefination,8 and direct nucleo-
philic substitution through use of vinyl halides.9 Despite their
usefulness, these approaches either require harsh reaction
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† National University of Singapore.
‡ Hebei University of Technology.
§ Hangzhou Normal University.
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10.1021/ol101729k  2010 American Chemical Society
Published on Web 08/20/2010

conditions, costly starting materials, and solvents or lack
stereocontrol at the double bond geometry.
arylpropiolic acids, resulting in stereoselective formation of
(Z)-vinyl sulfides under mild reaction conditions.
Phenylpropiolic acid (1a) and 4-methoxybenzenethiol (2a)
were used as the substrates to screen and optimize reaction
conditions. Copper(I) complexes generally gave significantly
higher yields of the product than copper(II) source (Table 1).
Numerous methods have been developed for the stereose-
lective synthesis of (E)-vinyl sulfides.10 In contrast, it has been
challenging to prepare Z-isomers.11 In 2005, Kondoh et al.12
reported the synthesis of (Z)-1-alkenyl sufides via a cesium-
catalyzed hydrothiolation of alkynes in the presence of 2,2,6,6-
tetramethylpiperidine-N-oxyl as a radical inhibitor. However,
this synthetic strategy is only applicable to alkylthiols. More
recently, Wang et al.13 have reported the synthesis of (Z)-1-
alkenyl sufides via a copper-catalyzed hydrothiolation of alkynes
with diaryl disulfides, but the reaction requires large amounts
of rongalite (4 equiv) as the radical initiator.
Table 1. Decarboxylative C-S Cross-Coupling under Different
Conditionsa
Recently, coupling reactions initiated by the decarboxy-
lation of carboxylic acids have shown great promise in the
field of synthetic chemistry.14 In particular, we have shown
that a broad range of aryl sulfides can be prepared through
decarboxylative C-S cross-coupling.15 Herein, we demon-
strate a novel copper-catalyzed decarboxylative thiolation of
entry catalyst (mol %)
1
base
KF
solvent yield of 3ab (%)
NMP
<5
57
74
88
77
35
0
2
3
4
5
6
7
8
9
CuI (20)
CuI (4)
CuI (4)
CuI (4)
CuI (4)
CuI (4)
CuI (4)
CuI (4)
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KHCO3
KF
piperidine NMP
TEA
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
DMSO
DMSO
NMP
PEG
DMF
toluene
dioxane
NMP
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5
77
10
30
5
10 CuI (20)
11 CuI (4)
12 CuI (4)
13 CuI (4)
14 CuCN (4)
15 CuCI (4)
16 CuBr (4)
17 CuCl2 (4)
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
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99(96)
85
80
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35
5
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Synlett 2007, 91.
18 CuCO3·Cu(OH)2 (4) Cs2CO3
19 Cu(OTf)2 (4) Cs2CO3
a All of the reactions were carried out with phenylpropiolic acid 1a
(0.5 mmol) and 4-methoxybenzenethiol 2a (0.75 mmol) in the presence of
a metal catalyst, NMP (3 mL), and base (1.2 equiv) at 90 °C for 24 h under
air atmosphere. b GC yield. Isolated yield is in parentheses.
40
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2005, 70, 6468.
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The amount of CuI can be decreased down to 4.0 mol %.
Different bases were screened, and the combination of cesium
carbonate with CuI afforded the best conversion efficiency
(Table 1, entry 13). In contrast to our previously reported
synthesis of aryl sulfides,15 we observe that palladium(II) is
not needed and milder reaction conditions are possible.
Under the optimal reaction conditions, a wide range of thiols
including aromatic, benzylic, and aliphatic thiols were examined
to react with phenylpropiolic acid via decarboxylative cross-
coupling reactions. The results are summarized in Table 2. We
observed that in the presence of the phenylpropiolic acid all
thiols afforded anti-Markovnikov coupling products in good
to excellent yields with high stereoselectivity for Z-isomers. The
arylthiols with electron-rich and electron-deficient aromatic
moieties were effectively converted to the corresponding vinyl
sulfides. Importantly, the decarboxylative coupling reactions are
tolerant of a broad range of functional groups including ethers,
amines, alcohols, halides, and nitrogen-containing heterocycles.
The functional group tolerance should enable further derivati-
zation of the as-synthesized vinyl sulfides (3k,o-s) through
cross-coupling reactions such as Suzuki-Miyaura, Sonogashira,
and Heck reactions.
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Org. Lett., Vol. 12, No. 18, 2010
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via different aryl-substituted alkynyl carboxylic acids (Table
3). All alkynyl carboxylic acids were converted into the
Table 2. Decarboxylative Cross-Coupling of Phenylpropiolic
Acid with Thiolsa
Table 3. Decarboxylative Cross-Coupling of Substituted
Phenylpropiolic Acids with Thiolsa
a All of the reactions were carried out with acids (0.5 mmol) and thiols
(0.75 mmol) in the presence of CuI (4.0 mol %) and Cs2CO3 (1.2 equiv) in
3 mL of NMP at 90 °C under air atmosphere. b Yields of isolated products
are the average of at least two experiments. c The Z/E ratio was based on
1
the analysis of H NMR spectra.
corresponding alkenyl sulfides in excellent yields. However,
alkynyl carboxylic acids with electron-withdrawing substit-
uents in the para position led to low stereoselectivity (entries
1, 2, and 4-7). In stark contrast, introduction of an electron-
donating group in the ortho-position resulted in the quantita-
tive formation of the corresponding Z-isomer (entry 3).
In summary, we have disclosed a copper-based decarboxylative
cross-coupling method for the synthesis of vinyl sulfides with high
stereoselectivity for Z-isomers. This method is important not only
for expanding our understanding of the decarboxylative reaction
but also for providing a convenient synthetic pathway for facile
synthesis of biologically or pharmaceutically relevant vinyl sulfide
compounds. Further investigations of the substrate scope of this
transformation and the reaction mechanism are currently in progress
in our laboratory.
Acknowledgment. This work was supported by ARF (R-
143-000-427-112). X.L. is grateful to the National University
of Singapore for a Young Investigator Award (R-143-000-318).
a All of the reactions were carried out with phenylpropiolic acids (0.5
mmol) and thiols (0.75 mmol) in the presence of CuI (4.0 mol %) and
Cs2CO3 (1.2 equiv) in 3 mL of NMP at 90 °C under air atmosphere. b Yields
of isolated products are the average of at least two experiments. c The Z/E
Supporting Information Available: Experimental pro-
cedures and spectroscopic data for all compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
1
ratio was based on the analysis of H NMR spectra.
To expand the scope of the general reaction conditions
further, we carried out decarboxylative C-S cross-coupling
OL101729K
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Org. Lett., Vol. 12, No. 18, 2010