3′-Substituted pyrimidines via alkylation-opening of 2,3′-cyclothymidine

Substituted thymidine derivatives are of interest because of their potential antiviral properties. We demonstrate a general strategy for synthesis of 3′-substituted thymidine derivatives, consisting of activation via N-3 alkylation of 2,3′-cyclothymidine followed by nucleophilic opening at the 3′-position. Examples include demonstration of carbon-carbon bond formation at the 3′-position.