Stereoselective Synthesis of 2-Deoxy-α-<i>O</i>-glycosides Enabled by Cobalt-Catalyzed Hydrogen Atom Transfer and Radical-Polar Crossover

We report a stereocontrolled glycosylation strategy for synthesizing 2-deoxy-α-O-glycosides via cobalt-catalyzed metal-hydride hydrogen atom transfer (MHAT) and radical-polar crossover (RPC) processes. This method achieves reagent-controlled stereoselectivity by modulating ligand environments, silane additives, and solvent effects, eliminating dependence on neighboring-group participation. Mechanistic studies reveal a sequence involving Co(III)–H-mediated hydrogen atom transfer, radical generation, and nucleophilic trapping of a Co(IV)–R intermediate to establish α-selectivity. Compared to conventional glycosylation protocols, this multitunable platform and chemoselectively compatible reaction conditions enable flexible 2-deoxy sugar assembly with extensive functional group tolerance, especially for substrates containing basic nitrogenous functional groups. The methodology provides a versatile and mild foundation for constructing structurally diverse glycoconjugates, including steroidal glycosides and nitrogen-containing acceptors such as ribonucleosides, deoxyribonucleosides, aniline, pyrrole, indole, and carbazole, demonstrating considerable potential for bioactive molecule development.