Diversification of Nucleosides Via Radical Mediated Deoxygenative Functionalization.

In this article we describe a general method for the synthesis of nucleoside derivatives bearing alkyl, cyano, and phosphate groups at the 3'-position or 2'-position. As exampled by thymidine and adenosine, this approach involves the installation of an activating reagent, 1,3-benzodithiol-2-ylium tetrafluoroborate (BDTF), at the 3'-hydroxy group of thymidine and 2'-hydroxy group of adenosine under mild conditions. Subsequent visible light promoted single-electron oxidation and β-scission generates the key radical intermediate and afford functionalized nucleosides by reaction with a broad range of radical acceptors. This method has the advantages of excellent yields and high diastereoselectivity, offering a versatile platform for the synthesis of complex, drug-relevant nucleoside derivatives. © 2026 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of 3'-O-BDT-thymidine and 2'-O-BDT-adenosine Basic Protocol 2: Deoxygenative functionalization of 3'-O-BDT-thymidine and 2'-O-BDT-adenosine.