Repurposing a supramolecular iridium catalyst via secondary Zn⋯OC weak interactions between the ligand and substrate leads to ortho-selective C(sp2)–H borylation of benzamides with unusual kinetics

Abstract

The iridium-catalyzed C–H borylation of benzamides typically leads to meta and para selectivities using state-of-the-art iridium-based N,N-chelating bipyridine ligands. However, reaching ortho selectivity patterns requires extensive trial-and-error screening via molecular design at the ligand first coordination sphere. Herein, we demonstrate that triazolylpyridines are excellent ligands for the selective iridium-catalyzed ortho C–H borylation of tertiary benzamides and, importantly, we demonstrate the almost negligible effect of the first coordination sphere in the selectivity, which is so far unprecedented in iridium C–H bond borylations. Remarkably, the activity is dramatically enhanced by exploiting a remote Zn⋯OC weak interaction between the substrate and a rationally designed molecular-recognition site in the catalyst. Kinetic studies and DFT calculations indicate that the iridium-catalyzed C–H activation step is not rate-determining, this being unique for remotely controlled C–H functionalizations. Consequently, a previously established supramolecular iridium catalyst designed for meta-borylation of pyridines is now compatible with the ortho-borylation of benzamides, a regioselectivity switch that is counter-intuitive regarding precedents in the literature. In addition, we highlight the role of the cyclohexene additive in avoiding the formation of undesired side-products as well as accelerating the HBpin release event that precedes the catalyst regeneration step, which is highly relevant for the design of powerful and selective iridium borylating catalysts.