Benzodithiolane‐Enabled C─O Bond Activation for Deoxygenative Functionalization of Carbohydrates and Nucleosides

ABSTRACT Carbohydrates and nucleosides are central to biological systems and medicinal chemistry, yet their selective chemical modification remains challenging. Although radical‐based deoxygenative strategies have emerged as powerful tools for carbohydrate functionalization, their extension to nucleosides, particularly at the C2′‐hydroxyl position, has remained largely unexplored. Here, we report a benzodithiolane (BDT) mediated C─O bond activation platform that enables deoxygenative functionalization of both carbohydrates and nucleosides under photoredox catalysis. The method accommodates structurally complex substrates, including unprotected derivatives, and supports diverse bond‐forming processes such as alkylation, vinylation, cyanation, and phosphonylation. Broad substrate scope, high functional‐group tolerance, and excellent stereocontrol are observed across a range of sugars and nucleosides. Mechanistic studies support a single‐electron‐transfer (SET)‐initiated radical pathway involving BDT‐assisted β‐scission as the key C─O bond cleavage event. By unlocking radical‐based C─O bond activation in previously inaccessible nucleoside substrates, this work establishes a versatile platform for the synthesis of C ‐glycosides, unconventional nucleosides and nucleoside–peptide conjugates.