Activation of 1-methylimidazole group-installed glycosyl ester donors with hydrogen-bond-forming (thio)urea catalysts

The activation of molecules through non-covalent interactions (NCIs), especially hydrogen bonds (HB) appears to be a successful strategy for constructing glycosidic linkages. Indisputably, thiourea-based organocatalysis demonstrates remarkable versatility in promoting selective glycosylation strategies through hydrogen bonding activation modes. In this study, we explore the use of glycosyl ester donors bearing a 1-methylimidazole moiety, which can be efficiently activated by charge-enhanced (thio)urea hydrogen-bond donor catalysts under mild conditions. This methodology enables the glycosylation of a wide array of nucleophiles, including natural products, glycosides, amino acids, and even weakly nucleophilic phenols via an operationally simple and mild protocol. Mechanistic investigations reveal that the (thio)urea catalyst forms a non-covalent complex with the donor through hydrogen bonding, facilitating the generation of a reactive glycosyl oxocarbenium ion intermediate. This intermediate subsequently engages with nucleophiles to form the desired glycosidic bond.