Amine-Enabled Open–Close Skeletal Editing of Aldoses to Access 1,2-cis C-Furanosides

Abstract C-glycosides are analogues of O-glycosides with broad relevance in drug discovery, yet their efficient synthesis from unprotected carbohydrates remains challenging. This Synpact highlights a bioinspired strategy that integrates the Petasis (borono–Mannich) reaction with an SN2-type deaminative cyclization, enabling the direct conversion of unprotected aldoses into C-glycosides bearing a 1,2-cis furanose framework. The method exploits stereospecific activation of C–N bonds to trigger intramolecular cyclization, delivering C-aryl and C-vinyl furanosides with high stereoselectivity and broad substrate scope. Mechanistic studies are consistent with an SN2 substitution pathway involving quaternary ammonium intermediates. The resulting C-vinyl furanosides exhibit versatile downstream reactivity, enabling rapid access to diverse C-alkyl glycoside derivatives and functional materials. This protecting-group-free approach provides a general platform for the stereoselective synthesis of C-glycoside architectures from readily available carbohydrates.