Enantioconvergent and Site-Selective Etherification of Carbohydrate Polyols through Chiral Copper Radical Catalysis

Going beyond currently reported two electron transformations that formed the core backdrop of asymmetric catalytic site-selective carbohydrate polyol functionalizations, we herein report a seminal demonstration of an enantioconvergent copper catalyzed site-selective etherification of minimally protected saccharides through a single-electron radical pathway. Further, this strategy paves a rare strategy, through which a carboxamide scaffold that is present in some glycomimetics of pharmacological relevance, can be selectively introduced. In light of the burgeoning interest in chiral radical catalysis, and the virtual absence of such stereocontrol broadly in carbohydrate synthesis, our strategy showcased the unknown capability of chiral radical copper catalysis as a contemporary tool to address the formidable site-selectivity challenge on a remarkable palette of naturally occurring saccharides. When reducing sugars were employed, a further dynamic kinetic resolution type glycosylation can be activated by the catalytic system to selectively generate the challenging beta-O-glycosides. By harnessing a chiral radical copper catalytic system, the challenging enantioconvergent and site-selective etherification of carbohydrate polyols is achieved. Besides being broadly applicable over a considerable range of sugars, multiple dimensions of stereocontrol can be tackled simultaneously. Remarkably, when anomeric unprotected reducing sugars were employed, dynamic kinetic resolution is further activated to achieve beta-O-glycosylation. image