Dehydroxylative Cross-Electrophile Coupling of Aromatic Acids with Glycosyl Chlorides Enables Rapid C -Acyl Glycoside Synthesis

Abstract

We disclose a synergistic nickel/photoredox/phosphoranyl radical catalytic platform for the cross-electrophile coupling of aromatic acids with glycosyl chlorides, affording structurally diverse C-acyl glycosides in a stereoselective manner directly from unactivated carboxylic acids. A key step involves the generation of phosphoranyl radicals via a polar/single-electron transfer crossover between a phosphine radical cation and aromatic acid, triggering homolytic cleavage of the strong C–O bond to yield acyl radicals. The method tolerates diverse aromatic acids, furanoses, and pyranoses and readily enables late-stage modification of pharmaceuticals, bioactive amino acids, and peptides, highlighting its utility in medicinal chemistry.