Site-Selective C−H Functionalization of Arenes Enabled by Noncovalent Interactions

Abstract

The direct metal-catalyzed C−H functionalization of arenes has emerged as a powerful tool for streamlining the synthesis of complex molecular scaffolds. However, despite the different chemical environments, the energy values of all C−H bonds are within a fairly narrow range; hence, the regioselective C−H bond functionalization poses a great challenge. The use of covalently bound directing groups is to date the most exploited approach to achieve regioselective C−H functionalization of arenes. However, the required installation and removal of those groups is a serious drawback. Recently, new strategies for regioselective metal-catalyzed distal C−H functionalization of arenes based on noncovalent forces (hydrogen bonds, Lewis acid−base interactions, ionic or electrostatic forces, etc.) have been developed to tackle these issues. Nowadays, these approaches have already showcased impressive advances. Therefore, the aim of this mini-review is to cover chronologically how these groundbreaking strategies evolved over the past decade.