Stereoselective synthesis of 1,2-annulated C-glycosides via palladium-catalyzed intramolecular annulation of C-aryl glycosides.

1,2-Annulated C-glycosides constitute an important class of structural motifs that appear in numerous biologically active natural products and therapeutic agents. Herein, we describe a ligand-free, intramolecular Pd-catalyzed annulation of C-aryl glycosides that enables the stereoselective synthesis of diverse 1,2-annulated C-glycosides. This strategy demonstrates the versatility of Pd catalysis in constructing fused carbohydrate frameworks under mild and tenable reaction conditions, allowing selective access to both six and five-membered annulated C-glycoside scaffolds. The method is operationally simple, scalable to gram quantities, and amenable to further synthetic elaboration, thereby providing a valuable platform for generating structurally complex glycoside derivatives with potential biological relevance. Control experiments and mechanistic investigations offer insight into the plausible reaction pathway governing the formation of these 1,2-annulated C-glycosides, highlighting the efficiency and synthetic utility of this annulation approach.