Diversification of Nucleosides Via Radical Mediated Deoxygenative Functionalization

Abstract

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