Photochemically Generated Sulfenylnitrene Unlocks Chemoselective Activation of Conventional Thioglycosides for Stereocontrolled Furanosylations

ABSTRACT The stereocontrolled construction of 1,2‐ cis furanosidic linkages remains a challenge in carbohydrate chemistry, as existing approaches often require multistep donor synthesis, anomerically pure precursors, and harsh activation conditions that compromise generality. Conventional thioglycosides are bench‐stable donors; however, their activation typically requires strong acids and cryogenic conditions, resulting in poor chemoselectivity, diminished stereocontrol, and epimerization to thermodynamically controlled 1,2‐ trans isomers. Here, we disclose a metal‐ and photosensitizer‐free photochemical strategy in which blue light promotes the chemoselective photolysis of an S─N bond in a sulfenylnitrene precursor, generating sulfenylnitrene that chemoselectively activates conventional thioglycosides. Sulfenylnitrene shows unique reactivity towards thioglycosides and remains unreactive with non‐glycosyl thioethers. This neutral process circumvents classical S N 2‐type pathways, enabling Lewis‐acid‐free and highly stereoselective furanosylations across ribose, arabinose, xylose, and the particularly challenging 2‐deoxyribose systems. Mechanistic investigations reveal that the steric and electronic effects of the C5‐protecting group induce the stereoselectivity. The synthetic utility of this platform is demonstrated by the efficient construction of glycosylated bioactive molecules and a 1,2‐ cis ribopentasaccharide. Overall, this work introduces sulfenylnitrene‐mediated activation as a sustainable and broadly applicable strategy for stereocontrolled furanosylation, expanding the conceptual scope of sulfur‐based nitrene chemistry in selective bond construction.