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 donors 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 S N 2 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.