A-RING OXYGENATION STUDIES IN BRIDGEHEAD HYDROXYL-SUBSTITUTED TRANS-TRICYCLO[9.3.1.03,8]PENTADECAN-14-ONE CONGENERS OF TAXOL

The ready availability of 5 has prompted examination of a convenient m eans for carbonyl transposition in its A-ring. Attempts to implement s uch chemistry directly on 5 and its silyl-protected derivative suffer from a kinetic proclivity for transannular capture of the enolate anio n. This undesirable process was circumvented by reduction of the C9 ca rbonyl following conversion to silyl enol ether 8. Once the resulting 9alpha-alcohol was protected as its MOM ether, the enolates of 10a and 10b could be efficiently oxygenated at C13 by treatment with the Davi s sulfonyl oxaziridine despite severe steric congestion in that locale . The resultant alpha-alcohol 11a could be epimerized to the 13beta-is omer by exposure to potassium hexamethyldisilazide. Remarkably, 11a is prone to autoxidation, although the yield of diketone 12 is capriciou s. A preferred route to this key intermediate involves periodinane oxi dation of 11a. Reduction of 12 and its O-silylated derivative has prov ided the targeted compounds 15 and 16, respectively. The conformationa l features of various intermediates are discussed in the light of NMR studies and MM2 calculations.