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

Therecently developed palladium-catalyzed C(sp(2))-Holefination of 2-arylbenzaldehyde with the aid of a temporary directinggroup (TDG) via reversible imine formation delivers selective meta-C-H functionalization and possesses significantadvantages over the well-established covalently attached directinggroup (DG) approach. In this report, a combined computational andexperimental investigation has been performed to elucidate the detailedreaction mechanism and the origins of such remote meta-selectivity. The reaction proceeds in three major steps: C-Hactivation, 1,2-migratory insertion, and & beta;-hydride elimination.While 1,2-migratory insertion of olefin is found to be the turnover-determiningstep, the selectivity is predetermined by the preceding C-Hactivation step. The computational observations have been corroboratedalong with experimentally conducted order determination studies, primarykinetic isotope effect (PKIE) study, and free energy correlation withHammett plots. A temporary DG-bound Pd complex has been shown to becompetent to promote meta-alkenylation. All the possiblePd-catalyzed template-directed C-H (ortho & PRIME;, ortho, meta, para) olefinations of the 2-aryl benzaldehyde/aniline have been computationallyinvestigated. The density functional theory (DFT)-based computationsindicated that the other olefination reactions necessitate higheractivation energy barriers compared with meta-olefination.Distortion-interaction analysis (DIA), noncovalent interaction (NCI)analysis, and isodesmic studies were executed to unravel the mysterybehind the origin of meta-regioselectivity.

Automated summary

This study investigates the palladium-catalyzed C(sp(2))-Holefination reaction of 2-arylbenzaldehyde with the aid of a temporary directing group. Computational and experimental methods are used to understand the reaction mechanism and selectivity. The results show that the reaction proceeds in three major steps and the selectivity is determined by the C-H activation step.