Synthesis of (±)-2′,3′-didehydro-2′,3′-dideoxy nucleosides via a modified Prins reaction and palladium(0) catalysed coupling

Abstract

Cyclopentenyl allylic acetates have been prepared in diastereoisomerically enriched form by modification of the Prins reaction. Palladium(0) catalysed coupling between these allylic acetates and a heteroaromatic base provides a highly convergent and direct route for synthesising carbocyclic 2′,3′-didehydro-2′,3′-dideoxy nucleosides. The method is exemplified by the coupling reaction with adenine which yields (±)-2′,3′-didehydro-2′,3′-dideoxyaristeromycin 5′-O-acetate 22 in 50% yield. This has been converted in two steps into (±)-aristeromycin triacetate 5.