Expanding the Scope of Group Transfer Radical Reaction: Toward the Synthesis of Fluorinated Nucleoside Analogues Incorporating Difluorophosphonylated Allylic Ether Moieties

Scope and limitations of the group transfer radical reaction of diisopropyl iododifluoromethylphosphonate onto carbohydrates and nucleosides are described. This key step allowed us to explore the synthesis of new fluorinated nucleoside analogues containing a difluorophosphonylated allylic ether moiety onto the 2'-position, in purine and pyrimidine series (B = A, C, G, T, U). Indeed, two unprecedented chemical approaches involving a late introduction of either the nucleobase or the fluorinated moiety are discussed.