Electrogenerated acid-catalyzed diastereoselective glycosylation with glycosyl acetates

Chemical glycosylation plays an indispensable role in the synthesis of bioactive glycans and glycoconjugates, which typically requires deliberate design of glycosyl donors and promoters. Here we report an efficient electrocatalytic glycosylation method employing readily available glycosyl acetates as donors. This protocol facilitates the rapid construction of diverse glycosides and disaccharides with moderate to high diastereoselectivity in an undivided cell under ambient conditions. Lithium perchlorate in acetonitrile was established as the optimal electrolyte/solvent system for this transformation. Mechanistic investigations demonstrate that the reaction proceeds through in situ generation of protonic acid at the anode surface, which catalyzes the cleavage of glycosyl acetates' C–O bonds. The method features broad substrate scope, accommodating a wide range of glycosyl acetate donors and acceptors, and enables efficient synthesis of various O -, S -, and N -glycosides.