Taxane Diterepenes 4: Autoxidation, Epimerisation and Isomerisation for the Introduction of Functionality into the Taxane ABC Ring System

The bicyclo[5.4.0]undecenone 4 was converted through a four step sequence involving activation, gem-methylcyclopropanation and reductive cleavage into 18 alpha/beta, containing the B/C rings of the taxanes. The A-ring has been attached to the B/C ring system by cyclization of the sulfone-ester 23 alpha to give 24. The A-ring was modified to give 29, which underwent beta-elimination of the 3,10-oxido bridge via a dianion, followed by transannular hydride shift to give the butenolide 30 and 32. Autoxidation of 30 gave 33 which was further elaborated into the trans-fused B/C adduct 35. The isomeric 3,10-diones trans-39 and cis-45 undergo autoxidation using t-BuOK/THF/O-2/P(OEt)(3) to give 2 and 46 respectively without B/C cis/trans isomerization. (C) 1998 Elsevier Science Ltd. All rights reserved.