Denitrogenative glycosylations of glycosyl sulfonohydrazides

Radical glycosylation has emerged as a powerful strategy in carbohydrate synthesis, offering alternative disconnections and direct functionalization of protected and native sugar. Despite notable progress, the development of novel and efficient glycosyl radical precursors that are readily accessible, synthetically versatile, and compatible with stereoselective coupling platforms remains an ongoing challenge. Here we report a nickelcatalysed stereoselective denitrogenative glycosylation of redox-neutral glycosyl sulfonohydrazides via anomeric C-N bond homolysis. Bench-stable (un)protected glycosyl sulfonohydrazides are concisely and catalytically synthesized via an open-closed ring equilibrium without stoichiometric reagents, and intrinsically generate glycosyl radicals without external redox additives, offering remarkable practical utility. This operationally simple, nickelcatalysed denitrogenative glycosylation platform-proceeding without photocatalysis-enables highly stereoselective formation of diverse C(sp³)-C(sp³), C(sp³)-C(sp²), C(sp³)-C(sp), C(sp³)-S, C(sp³)-Se, and C(sp³)-Te bonds, with broad substrate scope and excellent functional group tolerance. Importantly, this protecting-groupfree denitrogenative glycosylation provides straightforward access to a wide range of metabolically robust glycosyl derivatives. Mechanistic investigations proposed a nickel-catalysed radical pathway involving redox-neutral homolysis of Ni(II)-isodiazene complexes and thermally induced N₂ extrusion. Collectively, this work demonstrates that glycosyl sulfonohydrazides function as N-based glycosyl radical precursors, notably establishing a new class of unprotected glycosyl radicals while broadening the "cap-and-glycosylate" platform for glycomimetic synthesis and the glycodiversification of bioactive molecules.