Insights into the role of noncovalent interactions in distal functionalization of the aryl C(sp(2))–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(sp(2))–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 B(2)pin(2) (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 B(2)pin(2), 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 B(2)pin(2) 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.