AN ALLYLIC AZIDE ROUTE TO 4'-AZIDO CARBOCYCLIC NUCLEOSIDES - SYNTHESIS OF (+/-)-(1'ALPHA,2'ALPHA,3'BETA)- AND (+/-)-(1'ALPHA,2'BETA,3'BETA)-1-[1-AZIDO-2-HYDROXY-1-(HYDROXYMETHYL)-3-CYCLOPENTYL]THYMINE

Treatment of (+/-)-1-[[(tert-butyldiphenylsilyl)oxy]methyl]-3-methoxycyclopent-1-ene (17) with azidotrimethylsilane under Lewis acid catalyzed conditions gave an equilibrium mixture of allylic azides 18 and 19. Epoxidation of this mixture with peroxybenzimidic acid gave key epoxide (+/-)-(1alpha,2alpha,5alpha)-2-azido-2-[[tert-butyldiphenylsilyl)oxy]methyl]-6-oxabicyclo[3.1.0]hexane (5). Alternate routes designed to give tertiary azide precursors to 5 led to unanticipated products which are described. Title compound 28 was prepared by ring opening of 5 under Vorbruggen conditions followed by deprotection. Inversion of configuration at C-6' to give compound 30 was effected via O2,6'-cyclic intermediates 31 and 32. The relative stereochemistry of compounds in this series was suggested by NOE data for bromohydrins 23 and 26 and was confirmed by preparation of the fused oxetane 34.