C–OH Bond Activation for Stereoselective Radical C-Glycosylation of Native Saccharides

Abstract

Radical C-glycosylation presents a flexible and efficient method for synthesizing C-glycosides. Existing methods always require multistep processes for generating anomeric radicals. In this study, we introduce a streamlined approach to produce anomeric radicals through direct C–OH bond homolysis of unmodified saccharides, eliminating the need for protection, deprotection, or activation steps. These anomeric radicals selectively couple with activated alkenes, yielding C-glycosylation products with high stereoselectivity (>20:1). This method is applicable to a variety of native monosaccharides, such as l-arabinose, d-arabinose, d-xylose, l-xylose, d-galactose, β-d-glucose, α-d-glucose, and l-ribose, as well as oligosaccharides including α-lactose, d-(+)-melibiose, and acarbose. We also extend this approach to C-glycosylation of amino acid and peptide derivatives, and demonstrate a streamlined synthesis of an anti-inflammatory agent.