MACROLACTONIZATION-TRANSANNULAR ALDOL CONDENSATION APPROACH TO THE TAXANE AB RING-SYSTEM

Cyclohexenone 13, containing the fully elaborated taxane A ring, was prepared from 4,4-dimethyl-2-cyclohexenone (43% 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 (42% for three steps). Macrolactonization (59%) followed by chemoselective transannular aldol condensation within the resulting 11-membered bicyclic keto lactone 4 under thermodynamic control (51%) resulted in closure of the taxane B ring to afford the target 2(5H)-furanone 3.