Photoinduced 1,2-<i>cis</i> glycosidation with catalytic amounts of NIS : minimizing the requirements for donor activation and additive dependent anomeric stereocontrol

Abstract

We describe a simple and practical protocol utilizing 8% NIS in MTBE for efficient 1,2- cis glycosidations. 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 a blue LED. The proton of HI provides the donor activation and the iodide functions as an additive enabling 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 and circumvents the use of stoichiometric or excess amounts of promoters, specialized leaving groups or elaborate catalysts for donor activation and/or any supplementary additives and ligands for anomeric stereocontrol. As a sustainable approach, this glycosidation method represents a timely alternative for the chemical synthesis of complex carbohydrates.