Copper-promoted glycosylation using pyrrolidine-2-carboxylate-derived glycosyl donors

In this study, we report a series of pyrrolidine-based glycosyl ester donors for efficient glycosylation reactions. Among the donors investigated, carbamate-protected derivatives, especially glycosyl N-(tert-butoxycarbonyl) pyrrolidine-2-carboxylates, exhibited high reactivity, undergoing efficient activation under mild conditions in the presence of Cu(OTf)₂. The resulting donors possess a unique l-proline framework, can be prepared in a simple and practical manner through direct condensation of commercially available N-(tert-butoxycarbonyl)-l-proline with glycosyl hemiacetal derivatives and ease of use. The inexpensive Cu(OTf)₂ salt, enable high-yield glycosylation reactions with a broad range of acceptors. Moreover, their unique reactivity gradient facilitates efficient one-pot synthesis, highlighting their potential for diverse synthetic applications. Mechanistic studies suggest that donor activation proceeds through chelation-assisted coordination of the glycosyl ester donor with the metal cation, involving the carbonyl oxygen atoms of the ester and carbamate groups.