Computational Study of Ni-Catalyzed C–H Functionalization: Factors That Control the Competition of Oxidative Addition and Radical Pathways

The mechanisms of Ni-catalyzed C-H arylation, alkylation, and sulfenylation with N,N-bidentate directing groups are investigated using density functional theory (DFT) calculations. While the C-H cleavage occurs via the concerted metalation-deprotonation (CMD) mechanism in all types of reactions, the subsequent C-C and C-X bond formation steps may occur via either oxidative addition to form a Ni(IV) intermediate or radical pathways involving Ni(III) complexes generated from homolytic dissociation of disulfides/peroxides or halide-atom transfer from alkyl halides. DFT calculations revealed that radical mechanisms are preferred in reactions with sterically hindered coupling partners with relatively low bond dissociation energies (BDE) such as dicumyl peroxide, heptafluoroisopropyl iodide and diphenyl disulfide. In contrast, these radical processes are highly disfavored when generating unstable phenyl and primary alkyl radicals. In such cases, the reaction proceeds via an oxidative addition/reductive elimination mechanism involving a Ni(IV) intermediate. These theoretical insights into the substrate-controlled mechanisms in the C-H functionalizations were employed to investigate a number of experimental phenomena including substituent effects on reactivity, chemo- and regioselectivity and the effects of oxidant in the intermolecular oxidative C-H/C-H coupling reactions.