Switchable Synthesis of O - and C -Glycosides Enabled by Palladium-Catalyzed Chemodivergent Glycosylation

O-Glycosides and C-glycosides are privileged structural motifs in bioactive natural products and pharmaceuticals, yet their stereoselective synthesis from a common precursor remains a significant challenge. Herein, we report a reagent-controlled chemodivergent glycosylation enabling switchable synthesis of O- and C-glycosides from 4-keto-2,3-unsaturated glycosyl donors and arylboronic acids under open-air conditions. With the Pd(II)/phosphine ligand/base, O-glycosides are obtained in up to 90% yield (dr > 20:1); omission of the ligand and base redirects toward C-glycosides in up to 98% yield (dr > 20:1). The protocol accommodates diverse arylboronic acids and glycosyl donors with complete stereospecificity and is amenable to gram-scale synthesis and downstream functionalization to unprotected l-mannosides. Mechanistic studies reveal that both pathways proceed via Pd-π-allyl intermediates, diverging between an aerobic oxidation/Tsuji−Trost cascade for O-glycosylation and an outer-sphere boronate attack for C-glycosylation, providing a unified rationale for the observed switchable chemoselectivity and uniformly high diastereoselectivity.