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.