A Photoinduced, Nickel‐Catalyzed Reaction for the Stereoselective Assembly of C‐Linked Glycosides and Glycopeptides

Abstract

AbstractC‐Alkyl glycosides and glycoproteins exist in natural products and are prized for their role as carbohydrate mimics in drug design. However, a practical strategy that merges glycosyl donors with readily accessible reagents, derived from abundant carboxylic acid and amine feedstocks, is yet to be conceived. Herein, we show that a nickel catalyst promotes C−C coupling between glycosyl halides and aliphatic acids or primary amines (converted into redox‐active electrophiles in one step), in the presence of Hantzsch ester and LiI (or Et3N) under blue LED illumination to deliver C‐alkyl glycosides with high diastereoselectivity. Mechanistic studies support the photoinduced formation of alkyl radicals that react with a glycosyl nickel species generated in situ to facilitate cross‐coupling. Through this manifold, innate CO2H and NH2 motifs embedded within amino acids and oligopeptides are selectively capped and functionalized to afford glycopeptide conjugates through late‐stage glycosylation.