Copper-Catalyzed Synthesis of Vinyl Sulfides Craig G. Bates, Pranorm Saejueng, Michael Q. Doherty, and D. Venkataraman* Department of Chemistry, UniVersity of Massachusetts Amherst, 710 North Pleasant Street, Amherst, Massachusetts 01003 dV@chem.umass.edu Received October 27, 2004 ABSTRACT We report a method for the synthesis of vinyl sulfides using the soluble copper(I) catalyst [Cu(phen)(PPh 3 ) 2 ]NO 3 . The desired vinyl sulfides are obtained in good to excellent yields, with retention of stereochemistry. This protocol tolerates a wide variety of functional groups or substrates, is palladium-free, and does not require the use of expensive or air-sensitive additives. Vinyl sulfides play an important role as synthetic intermedi- ates in organic chemistry. They are used as equivalents of enolate ions 1 and Michael acceptors. 2 They are important intermediates in the synthesis of oxetanes, 3 cyclopentanones, 4 and cyclopentanes. 5 Many natural products and compounds exhibiting interesting biological properties contain the vinyl sulfide moiety. 6 Because of the importance of these compounds, there have been a number of reported methods for synthesizing vinyl sulfides. 7 The most noteworthy among them involves the addition of a thiol to an alkyne. This can occur either under radical conditions, 8 affording the anti-Markovnikov product containing a mixture of regioisomers, or through the employ- ment of transition metal catalysts (Mo, Pd, Pt, Rh, Ru). 9 The Wittig reaction has also been utilized in the synthesis of vinyl sulfides. 10 This approach requires the use of strong bases, and the synthesis of the appropriate Wittig reagents can be problematic. 7a Vinyl sulfides have also been prepared from the cross-coupling of vinyl halides and sodium or lithium benzenethiolates or their tin analogues. 11 However, the scope and functional group tolerance of these cross-coupling reactions have not been fully explored. (1) Trost, B. M.; Lavoie, A. C. J. Am. Chem. Soc. 1983, 105, 5075. (2) Miller, R. D.; Hassig, R. Tetrahedron Lett. 1985, 26, 2395. (3) Morris, T. H.; Smith, E. H.; Walsh, R. Chem. Commun. 1987, 964. (4) Magnus, P.; Quagliato, D. J. Org. Chem. 1985, 50, 1621. (5) (a) Mizuno, H.; Domon, K.; Masuya, K.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1999, 64, 2648. (b) Domon, K. M. K.; Tanino, K.; Kuwajima, I. Synlett 1996, 157. (6) (a) Sader, H. S.; Johnson, D. M.; Jones, R. N. Antimicrob. Agents Chemother. 2004, 48, 53. (b) Johannesson, P.; Lindeberg, G.; Johansson, A.; Nikiforovich, G. V.; Gogoll, A.; Synnergren, B.; Le Greves, M.; Nyberg, F.; Karlen, A.; Hallberg, A. J. Med. Chem. 2002, 45, 1767. (c) Ceruti, M.; Balliano, G.; Rocco, F.; Milla, P.; Arpicco, S.; Cattel, L.; Viola, F. Lipids 2001, 36, 629. (d) Marcantoni, E.; Massaccesi, M.; Petrini, M.; Bartoli, G.; Bellucci, M. C.; Bosco, M.; Sambri, L. J. Org. Chem. 2000, 65, 4553. (e) Lam, H. W.; Cooke, P. A.; Pattenden, G.; Bandaranayake, W. M.; Wickramasinghe, W. A. J. Chem. Soc., Perkin Trans. 1 1999, 847. (f) Morimoto, K.; Tsuji, K.; Iio, T.; Miyata, N.; Uchida, A.; Osawa, R.; Kitsutaka, H.; Takahashi, A. Carcinogenesis 1991, 12, 703. (7) (a) Zyk, N. V.; Beloglazkina, E. K.; Belova, M. A.; Dubinina, N. S. Russ. Chem. ReV. 2003, 72, 769 and references therein. (b) Kondo, T.; Mitsudo, T. Chem. ReV. 2000, 100, 3205. (8) (a) Beauchemin, A.; Gareau, Y. Phosphorus, Sulfur Silicon Relat. Elem. 1998, 139, 187. (b) Benati, L.; Capella, L.; Montevecchi, P. C.; Spagnolo, P. J. Chem. Soc., Perkin Trans. 1 1995, 1035. (c) Benati, L.; Montevecchi, P. C.; Spagnolo, P. J. Chem. Soc., Perkin Trans. 1 1991, 2103. (d) Ichinose, Y.; Wakamatsu, K.; Nozaki, K.; Birbaum, J. L.; Oshima, K.; Utimoto, K. Chem. Lett. 1987, 1647. (9) (a) Sugoh, K.; Kuniyasu, H.; Sugae, T.; Ohtaka, A.; Takai, Y.; Tanaka, A.; Machino, C.; Kambe, N.; Kurosawa, H. J. Am. Chem. Soc. 2001, 123, 5108. (b) Ogawa, A.; Ikeda, T.; Kimura, K.; Hirao, T. J. Am. Chem. Soc. 1999, 121, 5108. (c) Koelle, U.; Rietmann, C.; Tjoe, J.; Wagner, T.; Englert, U. Organometallics 1995, 14, 703. (d) Backvall, J. E.; Ericsson, A. J. Org. Chem. 1994, 59, 5850. (e) Kuniyasu, H.; Ogawa, A.; Sato, K. I.; Ryu, I.; Kambe, N.; Sonoda, N. J. Am. Chem. Soc. 1992, 114, 5902. (f) Mcdonald, J. W.; Corbin, J. L.; Newton, W. E. Inorg. Chem. 1976, 15, 2056. (10) (a) Aucagne, V.; Tatibouet, A.; Rollin, P. Tetrahedron 2004, 60, 1817. (b) Stephan, E.; Olaru, A.; Jaouen, G. Tetrahedron Lett. 1999, 40, 8571. (c) Ishida, M.; Iwata, T.; Yokoi, M.; Kaga, K.; Kato, S. Synthesis 1985, 632. (d) Mikolajczyk, M.; Grzejszczak, S.; Midura, W.; Zatorski, A. Synthesis 1975, 278. (e) Kumamoto, T.; Hosoi, K.; Mukaiyam, T. Bull. Chem. Soc. Jpn. 1968, 41, 2742. ORGANIC LETTERS 2004 Vol. 6, No. 26 5005-5008 10.1021/ol0477935 CCC: $27.50 © 2004 American Chemical Society Published on Web 12/02/2004