Photoinduced 1,2-cis Glycosidation with Catalytic Amounts of NIS: Minimizing the Requirements for Donor Activation and Additive Dependent Anomeric Stereocontrol

Abstract

Stereoselective glycosidation in a catalytic manner is one of the long-standing challenges in carbohydrate chemistry. Herein, an efficient and practical photo-induced glycosidation method is reported with O-gluco-, O-galacto- and O-xylopyranosyl trichloroacetimidates as donors and catalytic amounts of hydrogen iodide (HI) that is generated in situ from NIS and a hydrogen source by irradiation with blue LED. The proton of HI provides the donor activation and the iodide functions as additive enabling the anomeric stereocontrol. This way, a very convenient method for stereoselective glycosidation is provided. The method reliably affords 1,2-cis gluco-, galacto- and xylopyranosides from glycosyl donors and acceptors, bearing various functional groups, without necessitating additional additives or auxiliary directing groups. Notably, it has been successfully applied to the synthesis of an α-glucan tetrasaccharide. This metal-free experimentally simple glycosidation method expands the toolbox of stereoselective glycosidations that circumvent using stoichiometric or excess amounts of promoters, specialized leaving groups or elaborate catalysts for donor activation, and/or any supplementary additives and ligands for the anomeric stereocontrol. As a sustainable approach, this glycosidation method represents a timely alternative for the chemical synthesis of complex carbohydrates.