Harnessing Photochemically Generated Sulfenylnitrene for Stereocontrolled 1,2-cis Glycosylations

The stereocontrolled construction of 1,2-cis glycosidic linkages remains a persistent challenge, particularly in furanose systems, where planar oxocarbenium ions permit nucleophilic attack from either face. Conventional thioglycosides, although widely used, typically require harsh activation and often yield poor stereoselectivity. Here, we report a metal-free, photosensitizer-free, blue light-mediated strategy using sulfenylnitrenes as metallomimetic nitrene intermediates to activate thioglycoside donors chemoselectively. Sulfenylnitrene, produced by chemoselective photolysis of S–N bond, enables precise oxocarbenium ion formation, resulting in high 1,2-cis selectivity across ribose, xylose, glucose, galactose, mannose, and the challenging α-2-deoxyribosyl linkages. Cis selectivity is governed by C5–O protecting-group sterics and remotely participating group effects in furanoses, and by conformational locking in pyranoses. This approach allows the efficient synthesis of glycosyl esters, glycopeptides, glycosylated bioactive molecules, and rare 1,2-cis ribopentasaccharides. Notably, the donor design is broadly compatible with alternative activation methods, maintaining high selectivity, and provides a general blueprint for stereocontrolled glycosylation.