Macrolactonization-Transannular Aldol Condensation Approach to the Taxane AB Ring System

Article abstract of DOI:10.1021/jo00076a049

Cyclohexenone 13, containing the fully elaborated taxane A ring, was prepared from 4,4-dimethyl-2-cyclohexenone (43percent for four steps); two copper-catalyzed Grignard conjugate addition reactions on crowded dienones 8 and 11 were employed as key transformations.Elaboration of 13 to the chloro keto acid 6 was achieved via an epoxidation/regioselective chloride-mediated epoxide ring opening/Jones oxidation protocol (42percent for three steps).Macrolactonization (59percent) followed by chemoselective transannular aldol condensation within the resulting 11-membered bicyclic keto lactone 4 under thermodynamic control (51percent) resulted in closure of the taxane B ring to afford the target 2(5H)-furanone 3.