Deciphering the Mechanistic Insights of Temporary Directing-Group-Assisted meta-Alkenylation of Complex Biaryl Systems

The recently developed palladium-catalyzed C(sp 2 )–H olefination of 2-arylbenzaldehyde with the aid of a temporary directing group (TDG) via reversible imine formation delivers selective meta -C–H functionalization and possesses significant advantages over the well-established covalently attached directing group (DG) approach. In this report, a combined computational and experimental investigation has been performed to elucidate the detailed reaction mechanism and the origins of such remote meta -selectivity. The reaction proceeds in three major steps: C–H activation, 1,2-migratory insertion, and β-hydride elimination. While 1,2-migratory insertion of olefin is found to be the turnover-determining step, the selectivity is predetermined by the preceding C–H activation step. The computational observations have been corroborated along with experimentally conducted order determination studies, primary kinetic isotope effect (PKIE) study, and free energy correlation with Hammett plots. A temporary DG-bound Pd complex has been shown to be competent to promote meta -alkenylation. All the possible Pd-catalyzed template-directed C–H ( ortho′, ortho, meta, para ) olefinations of the 2-aryl benzaldehyde/aniline have been computationally investigated. The density functional theory (DFT)-based computations indicated that the other olefination reactions necessitate higher activation energy barriers compared with meta -olefination. Distortion-interaction analysis (DIA), noncovalent interaction (NCI) analysis, and isodesmic studies were executed to unravel the mystery behind the origin of meta -regioselectivity.