Site-selective Arene C-H Functionalization by Transition Metal/Lewis Acid Cooperative Catalysis

C-H functionalization has had significant attention in organic synthesis to streamline chemical processes of functional molecules. Efforts in the last two decades have allowed a variety of transformations, that had conventionally been performed with pre-functionalized compounds, to directly convert unfunctionalized C-H bonds to functional groups. A majority of these transformations, however, can be performed at limited sites in organic molecules. In the case of metalcatalyzed C-H functionalization, reaction sites of C-H functionalization are often controlled by directing groups, which coordinate to metals to bring the catalyst centers close to C-H bonds being transformed. Directing groups are often specially designed for certain C-H functionalization reactions, and they need additional steps for installation and uninstallation in addition to the C-H functionalizations. Such strategies limit the overall utility and efficiency of synthetic schemes involving C-H functionalization. It is highly desired that one can control the site-selectivity of C-H functionalization not by directing groups but by catalysts with compounds bearing common functional groups. We have taken advantages of catalytic Lewis-pair formations to electronically activate substrates and control the site-selectivity of transition metal-catalyzed C-H functionalization. In this article, C-C and C-B bond-forming reactions through C-H activation by cooperative transition metal/Lewis acid catalysis are described. Common Lewis acid catalysts derived from Zn, B, and Al are demonstrated to be highly efficient co-catalysts for Ni- and Ir-catalyzed arene C-H functionalization. Steric repulsion between the Lewis acids and Ni or Ir catalysts allows para-selective C-H functionalization, whereas ligands bearing such Lewis acid moieties are shown to be effective to control meta-selective C-H functionalization.

Automated summary

C-H functionalization is a key technique in organic synthesis to simplify chemical processes by converting unfunctionalized C-H bonds into functional groups. Traditionally, functionalization required pre-functionalized compounds, but now direct transformation is possible. However, current strategies using directing groups and additional steps limit efficiency, while a new approach utilizing Lewis acid-base formations to control site-selectivity of functionalization is being explored.