Streamlined Sugar Diversification via Photoredox‐Catalyzed Regio‐ and Stereoselective 1,2‐Alkylarylation of Glycals

Abstract Multi‐site modification of sugars represents a highly promising strategy for constructing bioactive molecules in glycosciences. However, the modular assembly of diversifiable sugar architectures from readily available precursors remains a considerable challenge. Here, we disclosed a photoredox‐catalyzed alkylarylation of glycals that achieves simultaneous diversification at the C1 and C2 positions of sugars. The reaction enables the synthesis of diverse 2‐ C ‐alkyl branched heteroaryl/aryl‐ C ‐glycosides, including unprotected ones, with excellent regio‐, site‐, and stereoselectivities, and is compatible with an array of (hetero)‐arenes and alkyl branches bearing a variety of functional groups. The utility is demonstrated through the gram‐scale synthesis and the efficient downstream modifications on the easily functionalizable C2 alkyl branches and the C1 (hetero)‐arenes, as well as the identification of a 2‐ C ‐alkyl phosphate aryl‐ C ‐glycoside as a potent antitumor agent through preliminary biological evaluation. A reaction mechanism is proposed based on radical trapping and Stern–Volmer luminescence experiments. Collectively, this study developed a modular, dual‐functional sugar diversification platform that facilitates simultaneous C sp 3 ─C sp 2 and C sp 3 ─C sp 3 bond formation at the saccharide skeleton, which represents an alternative strategy for the rapid construction of complex carbohydrate derivatives for drug discovery.