Computational rationalization of the selective C–H and C–F activations of fluoroaromatic imines and ketones by cobalt complexes

Abstract

While selective C–H and C–F activations of fluoroaromatic imines and ketones with transition metal complexes supported by PMe₃ have been successfully achieved in recent publications, insight into the molecular mechanism and energetics of those reactions is still lacking. Focusing on three typical substrates, 2,6-difluorobenzophenone imine (A) and 2,6-difluorobenzophenone (B), and 2,4′-difluorobenzophenone (C), the present work theoretically studied their C–H and C–F cyclometalation reactions promoted by the activator Co(PMe₃)₄ or CoMe(PMe₃)₄. It is found that reaction A + Co(PMe₃)₄ favors the C–F activation, reaction A + CoMe(PMe₃)₄ prefers the C–H activation, whereas both the C–H and C–F activation pathways may be viable for reactions B + CoMe(PMe₃)₄ and C + CoMe(PMe₃)₄. The experimentally observed C–H and C–F cyclometalation products have been rationalized by analyzing the thermodynamic and kinetic properties of two activation pathways. From calculated results combined with the experimental observations, we believe that three factors, i.e. the oxidation state of the metal center in the activators, the anchoring group of substrates, and substituted fluoroatom counts of the aromatic ring in substrates, affect the selectivity of C–H and C–F activations of fluoroaromatic ketones and imines. Calculated results are enlightening about the rational design of activators and substrates of fluoroaromatic imines and ketones to obtain the exclusive C–H or C–F bond activation product.