Copper-Mediated Radical Transformation of Protection-Free Glycosylsulfonohydrazide for Access to Diverse Glycosides

Protecting-group-free glycosides, which serve as fundamental scaffolds for numerous therapeutic agents, present significant synthetic challenges due to the difficulties in stereocontrol and the reliance on multistep protection–deprotection sequences. Herein, we report a unified and concise strategy that enables the highly stereoselective synthesis of diverse protecting-group-free glycosides─including alkenyl C -glycosides with multiple stereocenters, alkyl C -glycosides, aryl thioglycosides, and aryl selenoglycosides─that were previously difficult to access from unprotected glycosyl donors. The process involves generating glycosyl radicals from readily accessible glycosylsulfonohydrazides under copper/ligand/base mediation, which then undergo addition to various radicals or unsaturated bonds with high stereoselectivity. Notably, nitrogen-containing ligands are key to achieving highly stereoselective alkenyl glycosides and alkyl thioglycosides. The utility of this approach is demonstrated by the concise synthesis of an anti-inflammatory drug, highlighting its potential to accelerate the development of glycoside-based therapeutics.