Nitrene-mediated glycosylation with thioglycoside donors under metal catalysis.

Glycosylation chemistry plays a pivotal role in glycoscience. Recent substantial developments have poised the field to address emerging challenges related to sustainability, cost efficiency, and robust applicability in complex substrate settings. The transition from stoichiometric activation to metal-catalyzed methods promises enhanced chemoselectivity and greater precision in controlling glycosidic bond breakage and formation, key to overcoming existing obstacles. Here, we report a nitrene-mediated glycosylation strategy using regular aryl sulfide glycosyl donors and easily accessible 3-methyl dioxazolone as an activator under the catalysis of iron or ruthenium. The iron-catalyzed system demonstrates exceptional catalytic reactivity, requiring as little as 0.1 mole % of catalyst at room temperature, and works well for complex peptide substrates. The ruthenium-catalyzed system can accommodate acid-sensitive functional groups and challenging low-reactivity acceptors. Mechanistic investigations have unveiled unusual multistep pathways involving sulfur imidation of sulfide donors via nitrene transfer and sulfur-to-oxygen rearrangement of -acyl sulfilimines for the nitrene-mediated activation of sulfide donors.