Lewis Acid-Mediated Domino Glycosylation/Cyclization of Substituted Glycals: A Stereoselective Route Toward the Synthesis of 1,2-Annulated C-Glycosides

Annulated C-glycosides are widely recognized for their natural abundance and diverse bioactivity. Traditional synthesis emphasizes stereoselective α/β C-glycoside formation, but efficiently engaging both reactive carbons of glycosyl donors remains challenging. This study introduces a novel domino sequence using substituted glycals and β-naphthols under Lewis acid catalysis, generating glycosylated intermediates that undergo cascade reactions to yield annulated 1,2-C-glycosides. The method features a broad substrate scope, mild conditions, and versatility. Notably, annulation type varies with substituted glycals, yielding [3 + 2] or [3 + 3] fused pyran systems. Control experiments and DFT calculations provide mechanistic insights into substrate-specific product formation.