Ligand-Enabled Pd(II)-Catalyzed β-Methylene C(sp3)–H Arylation of Free Aliphatic Acids

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.