Glycosylation chemistry, a cornerstone of glycoscience, has witnessed substantial advancements over the past century. These developments have poised the field to tackle complex challenges related to sustainability, cost efficiency, and robust applicability, particularly in the modification of complex and delicate biorelevant substrates. Traditional glycosylation methods, often reliant on stoichiometric promoters and relatively harsh conditions, have faced inherent limitations. In response, metal catalysis has emerged as a more refined approach, offering enhanced control over glycosidic bond cleavage and formation under milder conditions. Sulfide glycosyl donors, known for their accessibility, are widely used in classical glycosylation reactions and show promise in metal-catalyzed variants. Traditional methods using these donors typically involve excess amounts of thiophilic metal complexes or combinations of potent electrophiles such as halonium ions with strong acid additives such as triflic acid (TfOH). Although effective with simple substrates, these approaches often struggle with compatibility when applied to more complex substrates containing acid-labile functional groups or strongly Lewis basic sites.

Recently, Hao Wang & Gong Chen’s group have reported 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 N-acyl sulfilimines for the nitrene-mediated activation of sulfide donors. Relevant achievements were published in Sci. Adv., 2025. DOI: 10.1126/sciadv.adu7747.