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

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.