Pd(II)-Catalyzed Synthesis of Benzocyclobutenes by β-Methylene-Selective C(sp <sup>3</sup> )–H Arylation with a Transient Directing Group
Philip Provencher, John Hoskin, Jonathan J. Wong, Xiangyang Chen, Jin‐Quan Yu, K. N. Houk, Erik J. Sorensen
Abstract
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.
Topics & Concepts
ChemistryMethyleneDeprotonationCatalysisIntramolecular forceSelectivityMetalationMedicinal chemistrySurface modificationLigand (biochemistry)StereochemistryOrganic chemistryIonPhysical chemistryReceptorBiochemistryCatalytic C–H Functionalization MethodsCatalytic Cross-Coupling ReactionsAsymmetric Hydrogenation and Catalysis