Stereoselective oxidative glycosylation of anomeric nucleophiles with alcohols and carboxylic acids.

Abstract

Oligosaccharides, one of the most abundant biopolymers, are involved in numerous biological processes. Although many efforts have been put in preparative carbohydrate chemistry, achieving optimal anomeric and regioselectivities remains challenging. Herein we describe an oxidative glycosylation method between anomeric stannanes and oxygen nucleophiles resulting in the formation of a C-O bond with consistently high anomeric control for glycosyl donors bearing a free C2-hydroxyl group. These reactions are promoted by hypervalent iodine reagents with catalytic or stoichiometric amounts of Cu or Zn salts. The generality of this transformation is demonstrated in 42 examples. Mechanistic studies indicate that the oxidative glycosylation is initiated by the hydroxyl-guided delivery of the hypervalent iodine and tosylate into the anomeric position, and results in excellent 1,2-trans selectivity. The unique mechanistic paradigm, high selectivities, and mild reaction conditions make this method suitable for the synthesis of oligosaccharides and for integration with other methodologies such as automated synthesis.