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.