Fast and Selective β-C-H Borylation of N-Heterocycles with a Supramolecular Iridium Catalyst: Circumventing Deactivation Pathways and Mechanistic Insights

Selectiveiridium-catalyzed C-H bond borylations of unbiasedor directing-group-free substrates typically occur under long reactiontimes and mild temperatures in order to avoid unselective processesincluding catalyst deactivation. Herein, we describe a supramolecularapproach that enables the C-H bond borylation of challengingpyiridines and imidazoles in very short reaction times (up to 2 h)with a negligible incubation period for catalyst activation. The catalystis based on a highly rigid zinc-porphyrin substrate-recognitionsite in the secondary coordination sphere and a triazolopyridine chelatingfragment attached to the first coordination sphere at iridium. Theborylation occurs at the C-H bond from the substrate locatedat four chemical bonds apart from the molecular recognition site withthe selectivity being exclusively imposed by the distance betweenthe active site and the molecular recognition site regardless of thenature of the N,N-chelating fragmentcoordinating to iridium as further supported by density functionaltheory (DFT) calculations. Additional studies (control experiments,nuclear magnetic resonance, and single-crystal X-ray diffraction)unraveled key catalyst deactivation pathways in which up to threedifferent partners (water, methoxide ligands from the iridium precursor,and the triazolopyridine fragment) compete with the N-heterocyclesubstrate for binding to the molecular recognition site of the supramolecularcatalyst. This fundamental understanding made possible the identificationof a supramolecular catalyst featuring a 4-methyl substitution patternin the first coordination sphere at iridium that provides a suitablebalance of steric and electronic effects in both primary and secondarycoordination spheres, thereby bypassing the manifold catalyst deactivationpathways. DFT calculations further indicated the importance of noncovalentinteractions beyond the molecular recognition site on the stabilizationof the different intermediates and transition sates.