Site-selective Arene C–H Functionalization by Cooperative Metal Catalysis

Abstract

Efforts made over the past three decades have led to the development of various organic transformations that directly convert unfunctionalized C–H bonds into functional groups by metal catalysis. However, many of these transformations are restricted to specific reaction sites controlled by directing groups, which bring the metal centers into proximity with the C–H bonds being functionalized. These directing groups are typically tailored for specific C–H functionalization reactions, necessitating additional steps for their installation and removal, thereby limiting overall utility and efficiency. There is a strong desire to achieve site-selectivity control using catalysts with compounds bearing common functional groups. We have investigated catalytic Lewis-pair formations to electronically activate substrates and control the site-selectivity of metal-catalyzed arene C–H functionalization. In this account, we present C–C and C–B bond-forming reactions through cooperative transition metal/Lewis acid (LA) catalysis. Common Lewis acid catalysts derived from Zn, B, and Al have been demonstrated as highly efficient co-catalysts for Ni- and Ir-catalyzed arene C–H functionalization. Steric repulsion between the LA and Ni or Ir catalysts facilitates para-selective C–H functionalization, while ligands bearing such Lewis acid moieties effectively control meta-selectivity.