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Synthesis of vinyl sulfides

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Palladium complexes derived from inexpensive dppf ligand catalyze the cross-coupling reaction of alkenyl bromides with thiols under low catalyst loading. These reactions occur in high yields and display wide scope, including the coupling of bulky thiols and trisubstituted bromoolefins, and functional group tolerance. In addition, a thioetherification of less reactive chloroalkenes and alkenyl tosylates has also been achieved.
N. Velasco, C. Virumbrales, R. Sanz, S. Suárez-Pantiga, M. A. Fernández-Rodríguez, Org. Lett., 2018, 20, 2848-2852.

A simple and efficient protocol for the cross-coupling of vinyl halides with thiols catalyzed by recyclable CuO nanoparticles under ligand-free conditions allows the synthesis of a various vinyl sulfides in excellent yields with retention of stereochemistry.
V. P. Reddy, K. Swapna, A. V. Kumar, K. R. Rao, Synlett, 2009, 2777-2782.

A mild, versatile, palladium-free method for the synthesis of vinyl sulfides using the soluble copper(I) catalyst [Cu(phen)(PPh3)2]NO3 is reported. The desired vinyl sulfides are obtained with retention of stereochemistry in good to excellent yields.
C. G. Bates, P. Saejueng, M. Q. Doherty, D. Venkataraman, Org. Lett., 2004, 6, 5005-5008.

cis-1,2-Cyclohexanediol is an efficient and versatile bidentate O-donor ligand that provides a highly active Cu-catalytic system for cross-coupling reactions of alkyl, aryl, or heterocyclic thiols with either alkyl, aryl, heterocyclic, or substituted vinyl halides. This new catalytic system promoted the mild and efficient stereo- and regiospecific synthesis of biologically important vinyl sulfides.
M. S. Kabir, M. Lorenz, M. L. V. Linn, O. A. Namjoshi, S. Ara, J. M. Cook, J. Org. Chem., 2010, 75, 3626-3643.

A nickel catalyzed CS cross-coupling of aryl and alkenyl triflates with alkyl thiols provides a variety of thioethers under mild reaction conditions in short reaction time using an air-stable nickel precatalyst. The reaction offers a broad substrate scope, including pharmaceutically relevant compounds.
R. M. Oechsner, I. H. Lindenmaier, I. Fleischer, Org. Lett., 2023, 25, 1655-1660.

A convenient Ni-catalyzed cross-coupling of inactivated or β-aryl-substituted (E)-alkenyl halides with thio-alcohols/phenols provides alkenyl sulfides in good yields. This alkenyl thioetherification is run under mildly basic conditions, that facilitate access to a broad range of products including protected amino acids, saccharides, and heterocycles.
B. Xu, H. Xiang, Y. Tan, Z. Li, S. Li, X.-Y. Ye, Y. Ye, J. Org. Chem., 2023, 88, 4592-4605.

The use of β-sulfinylesters as versatile sulfur source enables direct C(sp)-, C(sp2)-, and C(sp3)-H thiolation reactions. The desired products are formed via chemoselective retro-Michael C-S bond cleavage of sulfonium salts that are formed in situ from the corresponding alkenes, alkynes, and 1,3-dicarboxyl compounds with β-sulfinylesters.
Y. Chen, S. Wen, Q. Tian, Y. Zhang, G. Cheng, Org. Lett., 2021, 23, 7905-7909.

S-Alkyl, S-aryl, and S-vinyl thiosulfate sodium salts (Bunte salts), which can readily be prepared from sodium thiosulfate, react with Grignard reagents to give sulfides in good yields. The reaction is amenable to a broad structural array of Bunte salts and Grignard reagents. Importantly, this route to sulfides avoids the use of malodorous thiol starting materials or byproducts.
J. T. Reeves, K. Camara, Z. S. Han, Y. Xu, H. Lee, C. A. Busacca, C. H. Senanayaka, Org. Lett., 2014, 16, 1196-1199.

Indium tri(organothiolate) derivatives are effective nucleophilic coupling partners in Pd-catalyzed C-S crosscoupling reactions to produce functionalized sulfides in excellent yields with high atom efficiency and complete regio- and chemoselectivity.
J.-Y. Lee, P. H. Lee, J. Org. Chem., 2008, 73, 7413-7416.

The coupling of vinyl bromides with thiols or diphenyl diselenide using copper(I) salts as catalysts in ionic liquids based on amino acids gives vinyl chalcogenides in good to excellent yields with retention of stereochemistry. The ionic liquids act as solvent, base, and excellent promoter for the copper-catalyzed coupling reactions.
Z. Wang, H. Mo, W. Bao, Synlett, 2007, 91-94.

The use of NiI2 as an air-stable Ni(II) precatalyst, and P(OiPr)3 as a cheap and commercially available ligand enables a scalable and robust cross-coupling of various thiophenols with styryl bromides, including some sterically encumbered thiols, an α-bromocinnamaldehyde as well as a thiolation-cyclization.
A. D. Marchese, B. Mirabi, E. M. Larin, M. Lautens, Synthesis, 2020, 52, 311-319.

A hydrothiolation of aromatic alkynes with thiophenols by anti-Markonikov addition in the presence of β-cyclodextrin in water gives E-vinyl sulfides in excellent yields. β-Cyclodextrin can be recovered and reused for a number of runs without any loss of activity.
R. Sridhar, K. Surendra, N. S. Krishnaveni, B. Srinivas, K. R. Rao, Synlett, 2006, 3495-3497.

Stereoselectivity in copper-catalyzed hydrothiolation of alkynes is determined by the presence/absence of a CO2 atmosphere. The reaction system is robust and utilizes inexpensive, readily available substrates. A cyclic alkene/carboxylate copper complex intermediate is proposed as the key step, and an equivalent amount of water is found to play an active role as a proton donor.
S. N. Riduan, J. Y. Ying, Y. Zhang, Org. Lett., 2012, 14, 1761-1767.

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 via a decarboxylative cross-coupling.
S. Ranjit, Z. Duan, P. Zhang, X. Liu, Org. Lett., 2010, 12, 4134-4136.

The reaction of an alkyne with an alkanethiol in the presence of a catalytic amount of cesium carbonate and TEMPO as a radical inhibitor in DMSO provides the corresponding 1-alkenyl alkyl sulfide adduct in good yield with high Z-selectivity.
A. Kondoh, K. Takami, H. Yorimitsu, K. Oshima, J. Org. Chem., 2005, 70, 6468-6473.

Tp*Rh(PPh3)2 (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate) is a highly active catalyst for alkyne hydrothiolation with alkyl and aryl thiols. Hydrothiolation using alkyl thiols proceeds with excellent regioselectivity, providing convenient access to branched alkyl vinyl sulfides. A mixture of regioisomers is obtained when using aryl thiols.
C. Cao, L. R. Fraser, J. A. Love, J. Am. Chem. Soc., 2005, 127, 17614-17615.

Unsymmetrical internal alkynes such as ethyl phenylpropiolate successfully underwent Pt-catalyzed decarbonylative arylthiolation by thioesters.
F. Yamashita, H. Kuniyasu, J. Terao, N. Kambe, Org. Lett., 2008, 10, 101-104.

With CuI as the catalyst and K3PO4 • 3 H2O as the base, a highly efficient, ligand-free intramolecular S-vinylation of thiols with vinyl chlorides or bromides was successfully implemented. Moreover, competition experiments revealed that the 4-exo cyclization is fundamentally preferred over other modes (5-exo, 6-exo, and 6-endo) of cyclization.
Q. Zhao, L. Li, Y. Fang, D. Sun, C. Li, J. Org. Chem., 2009, 74, 459-462.

Air-stable palladium complexes with phosphinous acid ligands serve as efficient catalysts for various cross-coupling reactions of vinyl and aryl chlorides with arylboronic acids, arylzinc reagents, and thiols.
G. Y. Li, J. Org. Chem., 2002, 67, 3643-3650.


An alkoxy base promotes the conversion of aryl and alkenyl sulfonium triflates with diverse functionalities into vinyl sulfides with excellent reactivity under metal-free condition. This efficient transformation offers mild and safe reaction conditions that avoid catalyst, transition metal, high-pressure gas, and high reaction temperature.
P. Gao, Q. Zhang, F. Chen, Org. Lett., 2022, 24, 7769-7773.

2,2-Diphenyl-1,3-oxathiolane slowly liberates a vinyl sulfide anion under basic conditions, that can be effectively used in Pd/Xantphos-catalyzed reactions with a wide range of aryl bromides to provide aryl vinyl sulfides.
J. R. Schmink, S. A. B. Dockrey, T. Zhang, N. Chebet, A. van Venrooy, M. Sexton, S. I. Lew, S. Chou, A. Okazaki, Org. Lett., 2016, 18, 6360-6363.

A highly regio- and stereoselective coupling of (Z)-1,2-bis(aryl(alkyl)thio)alkenes and Grignard reagents in the presence of a Ni catalyst under mild conditions enables an efficient route for the synthesis of (Z)-vinylic sulfides. (Z)-vinylic sulfides are important intermediates in the synthesis of tri- and tetrasubstituted alkenes.
J. Chen, S. Chen, X. Xu, Z. Tang, C.-T. Au, R. Qiu, J. Org. Chem., 2016, 81, 3246-3255.

Tetraphosphine cis,cis,cis-1,2,3,4-tetrakis[(diphenylphosphino)methyl]cyclopentane (Tedicyp) is an efficient ligand for the Heck reaction of sulfur-containing alkenes with aryl bromides. The rates and yields of the reactions strongly depend on the oxidation state of the sulfur atom.
A. Battace, T. Zair, H. Doucet, M. Santelli, Synthesis, 2006, 3495-3505.

The reaction of 1-alkynyl sulfides and alkynyl sulfoxides with Et3Al in the presence of Cp2ZrCl2 as catalyst provides trisubstituted 1-alkenyl sulfides in good yields with high regio- and stereoselectivity. Depending on the equivalents of Et3Al, 1-alkynyl sulfoxides can also be reduced to 1-alkynyl sulfides.
R. N. Kadikova, I. R. Ramazanov, A. V. Vyatkin, U. M. Dzehmilev, Synthesis, 2018, 50, 1773-1775.

N-Alkynylthio phthalimides can be easily prepared in three steps from commercially available phthalimide and silver acetylides. N-Alkynylthio phthalimides are efficient electrophilic alkynylthiolating reagents that can react with various C-nucleophiles, including β-ketoesters, aryl boronic acids, and Grignard reagents to afford a diverse range of alkynyl thioethers under mild conditions.
W.-C. Gao, Y.-Z. Shang, H.-H. Chang, X. Li, W.-L. Wei, X.-Z. Yu, R. Zhou, Org. Lett., 2019, 21, 6021-6024.