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 SN2-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.
Singh et al. (Tue,) studied this question.