Glycosyl Aziridine Carbamates as Versatile Donors for Catalytically Activated Glycosylation

ABSTRACT Catalytically promoted glycosylation continues to pose challenges in carbohydrate synthesis, as glycosyl donors that tolerate multistep manipulations often require stoichiometric activation, whereas donors amenable to catalytic activation can exhibit excessive reactivity, higher cost, or synthetic complexity. Here we report a new class of glycosyl donors based on aziridine carbamates that combine high stability with efficient, metal‐free, catalytically mediated activation and a compact, atom‐economical leaving group. These donors are readily prepared, compatible with common protecting‐group manipulations, and selectively activated by catalytic amounts of TMSOTf. Experimental and DFT studies reveal that donor activation proceeds through nitrogen‐directed TMS + coordination, followed by selective aziridine N─C bond cleavage and an aziridine‐to‐oxazolidinone rearrangement that generates a reactive glycosyl oxonium species, constituting a strain‐release‐driven activation pathway. This platform supports a broad range of O ‐, S ‐, and N ‐glycosylation reactions across common and challenging substrates. Notably, the tunable reactivity of aziridine carbamate donors establishes well‐defined reactivity gradients relative to imidate and thioglycoside donors, enabling fully catalytic, orthogonal, and sequential one‐pot oligosaccharide synthesis under catalytic conditions, albeit currently requiring moderate promoter loadings. This work establishes aziridine carbamates as a mechanistically distinct and practical donor class for catalytic glycosylation.