A Biomimetic Procedure for the Synthesis of 1,2-cis C-Vinyl Furanosides from Unprotected Aldoses

C-glycosides are valuable analogs of O- and N-glycosides with broad pharmaceutical relevance. While most synthetic approaches to C-glycosides rely on protected glycosyl donors, there is growing interest in methods that utilize unprotected native sugars, particularly for synthesizing C-furanosides, which are thermodynamically less favored than their pyranosyl counterparts. Inspired by enzymatic biosynthesis, we report a biomimetic “open-and-close” strategy for the synthesis of 1,2-cis C-vinyl furanosides from unprotected aldoses. This process involves a morpholine-mediated Petasis reaction between aldoses and vinyl boronic acids, converting cyclic hemiacetals into linear polyhydroxy amines with high 1,2-anti selectivity. Subsequent difluorocarbene-induced deaminative cyclization efficiently forms the furanose ring with high chemoselectivity and diastereoselectivity. The method exhibits broad substrate scope, accommodating various vinyl boronic acids as well as native mono- and disaccharides, and is amenable to scale-up under mild, aqueous-compatible conditions. Downstream derivatizations of the vinyl group afford 1,2-cis C-alkyl furanosides, offering efficient access to otherwise challenging molecular architectures.