Catalytic Asymmetric Allylation of Ketones and a Tandem Asymmetric Allylation/Diastereoselective Epoxidation of Cyclic Enones Jeung Gon Kim, Karen M. Waltz, Iliana F. Garcia, David Kwiatkowski, and Patrick J. Walsh* Contribution from the P. Roy and Diana T. Vagelos Laboratories, Department of Chemistry, UniVersity of PennsylVania, 231 South 34th Street, Philadelphia, PennsylVania 19104-6323 Received April 19, 2004; E-mail: pwalsh@sas.upenn.edu Abstract: A simple procedure is reported for the catalytic asymmetric allylation of ketones, utilizing titanium tetraisopropoxide, BINOL, 2-propanol additive, and tetraallylstannane as allylating agent. A variety of ketone substrates, including acetophenone derivatives and R,-unsaturated cyclic enones, reacted to form tertiary homoallylic alcohols in good yields (67-99%) and with high levels of enantioselectivity (generally >80%). A novel one-pot enantioselective allylation/diastereoselective epoxidation has also been introduced. Thus, upon completion of the allyl addition to conjugated cyclic enones, 1 equiv of tert-butyl hydroperoxide is added and the directed epoxidation of the allylic double bond ensues to afford the epoxy alcohol with high diastereoselectivity. Introduction Catalytic asymmetric additions of carbon-based nucleophiles to carbonyl groups constitute an important class of C-C bond- forming reactions that are of great value in synthetic organic chemistry. 1-5 Many catalysts will efficiently promote such additions to aldehydes; however, in almost all cases, those same catalysts fail to exhibit similar levels of reactivity and enantio- selectivity with ketones. 1-5 As a result, the catalytic enantiose- lective synthesis of tertiary alcohols has remained a long- standing goal in asymmetric catalysis. 6 The synthetic potential of these challenging reactions has attracted considerable interest. Recent successes include efficient and highly enantioselective catalysts for the asymmetric addition of alkyl, 7-9 aryl, 10-13 and alkynyl 3,14,15 groups to ketones and alkyl 16,17 and alkynyl 18 groups to R-keto esters. 19 We have been actively involved in the development of catalysts for this class of reactions. 7-9,11,20 A related carbonyl addition reaction that has also attracted significant attention is the asymmetric allylation of aldehydes 21-37 and ketones. 4,5,37-40 The products of these reactions, secondary and tertiary homoallylic alcohols, are useful intermediates that have been used in organic synthesis. 41-48 Several closely related (1) Soai, K.; Niwa, S. Chem. ReV. 1992, 92, 833-856. (2) Pu, L.; Yu, H.-B. Chem. ReV. 2001, 101, 757-824. (3) Pu, L. Tetrahedron 2003, 59, 9873-9886. (4) Yanagisawa, A. In ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999; Vol. 2, pp 965- 979. (5) Denmark, S. E.; Fu, J. Chem. ReV. 2003, 103, 2763-2794. (6) Corey, E. J.; Guzman-Perez, A. Angew. Chem., Int. Ed. 1998, 37, 388- 401. (7) Garcı ´a, C.; LaRochelle, L. K.; Walsh, P. J. J. Am. Chem. Soc. 2002, 124, 10970-10971. (8) Jeon, S.-J.; Walsh, P. J. J. Am. Chem. Soc. 2003, 125, 9544-9545. (9) Betancort, J. M.; Garcı ´a, C.; Walsh, P. J. Synlett 2004, 749-760. (10) Dosa, P. I.; Fu, G. C. J. Am. Chem. Soc. 1998, 120, 445-446. (11) Garcı ´a, C.; Walsh, P. J. Org. Lett. 2003, 5, 3641-3644. (12) Li, H.; Garcı ´a, C. G.; Walsh, P. J. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5425-5427. (13) Prieto, O.; Ramo ´n, D. J.; Yus, M. Tetrahedron: Asymmetry 2003, 14, 1955-1957. (14) Cozzi, P. G. Angew. Chem., Int. Ed. 2003, 42, 2895-2898. (15) Lu, G.; Li, X.; Jia, X.; Chan, W. L.; Chan, A. S. C. Angew. Chem., Int. Ed. 2003, 42, 5057-5058. (16) DiMauro, E. F.; Kozlowski, M. C. Org. Lett. 2002, 4, 3781-3784. (17) Funabashi, K.; Jachmann, M.; Kanai, M.; Shibasaki, M. Angew. Chem., Int. Ed. 2003, 42, 5489-5492. (18) Jiang, B.; Chen, Z.; Tang, X. Org. Lett. 2002, 4, 3451-3453. (19) Ramo ´n, D. J.; Yus, M. Angew. Chem., Int. Ed. 2004, 43, 284-287. (20) Waltz, K. M.; Gavenonis, J.; Walsh, P. J. Angew. Chem., Int. Ed. 2002, 41, 3697-3699. (21) Keck, G. E.; Tarbet, K.; Geraci, L. S. J. Am. Chem. Soc. 1993, 115, 8467- 8468. (22) Keck, G. E.; Krishnamurthy, D.; Grier, M. C. J. Org. Chem. 1993, 58, 6543-6544. (23) Keck, G. E.; Geraci, L. S. Tetrahedron Lett. 1993, 34, 7827-7828. (24) Costa, A. L.; Piazza, M. G.; Tagliavini, C.; Umani-Ronchi, A. J. Am. Chem. Soc. 1993, 115, 7001-7002. (25) Bedeschi, P.; Casolari, S.; Costa, A. L.; Tagliavini, E.; Umani-Ronchi, A. Tetrahedron Lett. 1995, 36, 7897-7900. (26) Weigand, S.; Bu ¨rckner, R. Chem.-Eur. J. 1996, 2, 1077-1084. (27) Faller, J. W.; Sams, D. W. I.; Lu, X. J. Am. Chem. Soc. 1996, 118, 1217- 1218. (28) Yanagisawa, A.; Nakashima, H.; Ishiba, A.; Yamamoto, H. J. Am. Chem. Soc. 1996, 118, 4723-4724. (29) Yu, C.-M.; Choi, H.-S.; Jung, W.-H.; Lee, S.-S. Tetrahedron Lett. 1996, 37, 7095-7098. (30) Casolari, S.; Cozzi, P. G.; Orioli, P.; Tagliavini, E.; Umani-Ronchi, A. J. Chem. Soc., Chem. Commun. 1997, 2123-2124. (31) Kii, S.; Maruoka, K. Tetrahedron Lett. 2001, 42, 1935-1939. (32) Yamago, S.; Furukawa, M.; Azuma, A.; Yoshida, J.-I. Tetrahedron Lett. 1998, 39, 3783-3786. (33) Doucet, H.; Santelli, M. Tetrahedron: Asymmetry 2000, 11, 4163-4169. (34) Zimmer, R.; Hain, U.; Berndt, M.; Gewald, R.; Reissig, H. U. Tetrahe- dron: Asymmetry 2000, 11, 879-887. (35) Hanawa, H.; Uraguchi, D.; Konishi, S.; Hashimoto, T.; Maruoka, K. Chem.- Eur. J. 2003, 9, 4405-4413. (36) Loh, T.-P.; Zhou, J.-R.; Yin, Z. Org. Lett. 1999, 1, 1855-1857. (37) Hanawa, H.; Kii, S.; Maruoka, K. AdV. Synth. Catal. 2001, 1, 57-60. (38) Casolari, S.; D’Addario, D.; Tagliavini, E. Org. Lett. 1999, 1, 1061-1063. (39) Yasuda, M.; Kitahara, N.; Fujibayashi, T.; Baba, A. Chem. Lett. 1998, 8, 743-744. (40) Yamasaki, S.; Fujii, K.; Wada, R.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2002, 124, 6536-6537. (41) Fu ¨rstner, A.; Langemann, K. J. Am. Chem. Soc. 1997, 119, 9130-9136. (42) Marshall, J. A.; Liao, J. L. J. Org. Chem. 1998, 63, 5962-5970. Published on Web 09/14/2004 12580 9 J. AM. CHEM. SOC. 2004, 126, 12580-12585 10.1021/ja047758t CCC: $27.50 © 2004 American Chemical Society