A Radical Activation Strategy for Versatile and Stereoselective N‐Glycosylation

Abstract

Previous N‐glycosylation approaches have predominately involved acidic conditions, facing challenges of low stereoselectivity and limited scope. Herein, we introduce a radical activation strategy that enables versatile and stereoselective N‐glycosylation using readily accessible glycosyl sulfinate as a donor under basic conditions and exhibits exceptional tolerance towards various N‐aglycones containing alkyl, aryl, heteroaryl and nucleobase functionalities. Preliminary mechanistic studies indicate a pivotal role of iodide, which orchestrates the formation of a glycosyl radical from the glycosyl sulfinate and subsequent generation of the key intermediate, a configurationally well‐defined glycosyl iodide, which is subsequently attacked by an N‐aglycone in a stereospecific SN2 manner to give the desired N‐glycosides. An alternative route involving the coupling of a glycosyl radical and a nitrogen‐centered radical is also proposed, affording the exclusive 1,2‐trans product. This novel approach promises to broaden the synthetic landscape of N‐glycosides, offering a powerful tool for the construction of complex glycosidic structures under mild conditions.