Stereo-Switchable Electrochemical Glycosylation

Stereoselective glycosylation reactions pose considerable challenges in organic synthesis, and electro-driven glycosylation remains largely underexplored. In this study, we introduce an electrochemical glycosylation reaction that uses glycosyl imidates to achieve switchable stereoselectivity through changes in electrolyte composition. This glycosylation method enables the synthesis of a diverse range of O-glycosides and oligosaccharides with excellent stereoselectivity, and yields up to 98%. In addition, we performed a comparative analysis of our method against conventional techniques and found that it significantly surpasses Lewis-acid-catalyzed methods in terms of selectivity and substrate applicability. Our method provides a broad substrate scope, excellent stereoselectivity, compatibility with various functional groups, scalability for the synthesis of oligosaccharides, and high yields. Experimental and computational mechanistic studies reveal the intermediacy of aminyl radical and the crucial role of the counterion and solvent in reversing stereoselectivity in distinct pathways. As such, it represents a robust platform for the controlled assembly of carbohydrates with high stereoselectivity and efficiency and is a compelling example of electrosynthesis.