We have already demonstrated that the asymmetric Heck reaction is a powerful method for the synthesis of various optically active carbon skeletons including derivatives of decalin, hydrindan, and bicyclo[3.3.0]octane. Here we would like to report the following. Bicyclic enone 1, a functionalized decalin derivative, has been synthesized in up to 86% ee by an asymmetric Heck reaction starting with bisallylic alcohol 20. Enone 1 has been converted to 28, a key intermediate in the synthesis of vernolepin (3). Furthermore, bicyclic dienone 2 has been synthesized in up to 83% ee from the prochiral dienone 19. The best conditions found employed Pd_2(dba)_3・CHCl_3 (9mol% of Pd) and (R)-BINAP (11.3mol%). With this catalyst and tert-BuOH as an additive, cyclization of 20 proceeded cleanly in dichloroethane at 60℃ to yield 1 in 86% ee and a chemical yield of 76%. With the same catalyst, cyclization of 19 proceeded in dichloroethane at 40℃ to yield 2 in 83% ee and a chemical yield of 66%. Having completed the asymmetric synthesis of enone 1, we have gone on to demonstrate the usefulness of enone 1 as a chiral building block. As shown in Scheme 6, 1 was converted to a key intermediate (-)-28 for Danishefsky's synthesis of vernolepin (3). Thus, our asymmetric synthesis of (-)-28 provides the first formal synthetic route to (+)-3.
