A Photoinduced, Nickel‐Catalyzed Reaction for the Stereoselective Assembly of <i>C‐</i>Linked Glycosides and Glycopeptides
Yi Wei, Quanquan Wang, Ming Joo Koh
Abstract
Abstract C ‐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 Et 3 N) 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 CO 2 H and NH 2 motifs embedded within amino acids and oligopeptides are selectively capped and functionalized to afford glycopeptide conjugates through late‐stage glycosylation.