Understanding the Regioselectivity of Ion-Pair-Assisted Meta-Selective C(sp2)–H Activation in Conformationally Flexible Arylammonium Salts

Abstract

The lack of directionality and the long-range nature of Coulomb interactions have been a bottleneck to achieve chemically precise C–H activation using ion-pairs. Recent report by Phipps and co-workers of the ion-pair-directed regioselective Iridium-catalyzed borylation opens a new direction toward harnessing noncovalent interactions for C–H activation. In this article, the mechanism and specific role of ion-pairing are investigated using density functional theory (DFT). Computational studies reveal that meta C–H activation is kinetically more favorable than the para analogue due to stronger electrostatic interactions between the ion-pairs in closer proximity [d(NMe3+···SO3–)TSP1m = 3.93 Å versus d(NMe3+···SO3–)TSP1p = 4.30 Å]. The electrostatic interactions overwhelm the Pauli repulsion and distortion interactions incurred in bringing the oppositely charged ions in close contact for the rate-limiting meta transition state (TSP1m). Multiple linear regression shows that the free energies of activation correlate well with descriptors like the charge densities on the meta carbon and Ir atom along with that on the cation and anion with R2 = 0.74. Tuned range-separated DFT calculations demonstrate accurately the localization of charge separation in the reactant complex and transition state for the meta selectivity.