Stereoselective C-Aryl Glycosylation by Catalytic Cross-Coupling of Heteroaryl Glycosyl Sulfones

Abstract

Stereoselective C-glycosylation reactions are increasingly gaining attention in carbohydrate chemistry because they enable glycosyl precursors, readily accessible as anomeric mixtures, to converge to a single diastereomeric product. However, controlling the stereochemical outcome through transition-metal catalysis remains challenging, and methods that leverage bench-stable heteroaryl glycosyl sulfone donors to facilitate glycosylation are rare. Herein, we show two complementary nonprecious metal catalytic systems, based on iron or nickel, which are capable of promoting efficient C-C coupling between heteroaryl glycosyl sulfones and aromatic nucleophiles or electrophiles through distinct mechanisms and modes of activation. Diverse C-aryl glycosides were secured with excellent selectivity, scope, and functional-group compatibility, and reliable access to both α and β isomers was possible for key sugar residues.

Keywords: C-Aryl Glycosides; Cross-Coupling; Glycosyl Sulfones; Iron Catalysis; Nickel Catalysis.