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Ligand-Enabled Pd(II)-Catalyzed β-Methylene C(sp3)-H Arylation of Free Aliphatic Acids
Liang Hu1, Guangrong Meng1, Jin-Quan Yu1
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Abstract:
Ligand development has enabled rapid advances in Pd(II)-catalyzed β-methyl C(sp3)-H activation of free carboxylic acids. However, there are only a handful of reports of free-acid-directed β-methylene C(sp3)-H activation, all of which are limited to intramolecular reactions. Herein, we report the first Pd(II)-catalyzed intermolecular β-methylene C(sp3)-H arylation of free aliphatic acids, which is enabled by bidentate pyridine-pyridone ligands. The bite angle of this ligand has been discovered to play a key role in promoting β-methylene C-H activation of free carboxylic acid. This new transformation provides a disconnection for alkylation of arenes with simple aliphatic acids. A variety of free aliphatic acids, including the antiasthmatic drug seratrodast, were compatible with the reported protocol.
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