Dehydroxylative Cross-Electrophile Coupling of Aromatic Acids with Glycosyl Chlorides Enables Rapid C-Acyl Glycoside
Chenchen Jiao1, Qingfeng Liu1, Lanfeng Shen1
1Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Key Laboratory for Green Media and Reactions, Henan International Joint Laboratory of Green Chemistry, Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan453007, P. R. China.
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.
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