Direct synthesis of 8-Fluoro purine Nucleosides via metalation-fluorination

A straightforward access to protected 8-fluoro nucleosides via metal ation - electrophilic fluorination under heterogeneous reaction conditions is reported. This is the first synthesis of 8-fluoro-2(')-deoxyribonucleoside derivatives. Phenylsulfonyl substituted nucleosides are accompanying byproducts, possibly indicating a competing radical process. Higher yields of 8-fluoro derivatives were obtained with 2(')-deoxyribonucleosides, as compared to ribonucleosides. Deprotection of the hydroxyl groups leading to 8-fluoro-2(')deoxyadenosine using TASF in methylene chloride demonstrates the compatibility of desilylation with 8-fluoro substituted nucleosides. NMR data indicate a syn conformation of the 8-fluoro derivatives.