Insights into the role of noncovalent interactions in distal functionalization of the aryl C(sp²)-H bond

Burgeoning interest in distal functionalization of aryl C-H bonds led to the development of iridium-catalyzed borylation reactions. The significance and inadequate mechanistic understanding of C(sp²)-H borylations motivated us to investigate the key catalytic steps and the origin of a directing-group-free regiocontrol in the reaction between aryl amides and B₂pin₂ (bis(pinacolato)diboron). An Ir(iii)(ubpy)tris(boryl) complex, generated from the pre-catalyst [Ir(OMe)(cod)]₂ by the action of a bipyridine-urea ligand (ubpy) and B₂pin₂, is considered as the most likely active catalyst. The meta C-H activation of N,N-dihexylbenzamide is energetically more favorable over the para isomer. The origin of this preference is traced to the presence of a concerted action of noncovalent interactions (NCIs), primarily between the catalyst and the substrate, in the regiocontrolling transition states (TSs). Molecular insights into such TSs revealed that the N-H···O interaction between the tethered urea moiety of the Ir-bound ubpy ligand of the catalyst and the amide carbonyl of the substrate is a critical interaction that helps orient the meta C-H bond nearer to iridium. Other NCIs such as C-H···π between the substrate and the catalyst, C-H···O involving the substrate C-H and the oxygen of the B₂pin₂ ligand and C-H···N between the substrate and the N atom of the Ir-bound ubpy confirm the significance of such interactions in providing the desirable differential energies between the competing TSs that form the basis of the extent of regioselectivity.