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

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.