Computationally designed ligands enable tunable borylation of remote C–H bonds in arenes

Abstract

<h2>Summary</h2> An ideal way to synthesize multi-substituted arenes is the selective installation of any group on any position of aromatic rings with any substituent. However, reactant-controlled selective functionalization of both <i>meta</i>- and <i>para</i>-C–H bonds is essentially impossible because of their intrinsically contradictory electronic and steric demands. Here, we report the first examples of catalysts that can direct the tunable borylation of a variety of arenes with precise control at either <i>meta</i> or <i>para</i> site through the computational design of ligands. A wide range of hydrogen bond acceptors can serve as directing groups, including Weinreb amides, phosphonates, and boronates, which can be easily transformed into many different types of functional groups. This work also showcases the critical role of transition-state calculations in catalyst design for remote C–H activation.