A versatile method to prepare difluorinated primary alcohols and its application to the syntheses of novel acyclic fluorinated nucleosides

Abstract

The addition of fluorine to a molecule often leads to intriguing changes in the properties of the molecule. Many novel drug leads and drug candidates are the results of the incorporation of fluorine. This Letter presents a versatile method to create molecules with the general structure R1R2CHCF2CH2OH from ketone R1(CO)R2. The key steps of this synthetic method involve the formation of a cyclic thiocarbonate and the regioselective radical opening of the thiocarbonate to yield the corresponding primary alcohol –CF2CH2OH. Using this synthetic method, novel fluorinated analogs of ganciclovir and penciclovir have been prepared.