Pd(II)-Catalyzed Synthesis of Benzocyclobutenes by β‑Methylene-Selective C(sp3)–H Arylation with a Transient Directing Group

Methylene-selective C–H functionalization is a significant hurdle that remains to be addressed in the field of Pd­(II) catalysis. We report a Pd­(II)-catalyzed synthesis of benzocyclobutenes by methylene-selective C­(sp3)–H arylation of ketones. The reaction utilizes glycine as a transient directing group and a 2-pyridone ligand, which may govern the methylene selectivity by making intimate molecular associations with the substrate during concerted metalation–deprotonation. This reaction is shown to be highly selective for intramolecular methylene C­(sp3)–H arylation, thus enabling sequential C­(sp3)–H functionalization.