Computational Mechanistic Study on the Nickel-Catalyzed C-H/N-H Oxidative Annulation of Aromatic Amides with Alkynes: The Role of the Nickel (0) Ate Complex

Density functional theory (DFT) was used to unveil intimate mechanistic insights on the monodentate-chelation system that is used in the Ni-catalyzed C-H/N-H oxidative annulation of aromatic amides with alkynes, a reaction that was originally reported by our group Chem Sci. 2017, 8, 6650-6655, DOI: 10.1039/C7SC01750B). The proposed reaction mechanism involves two reaction paths. The initial path is initiated by Ni(II), and the other, the main catalytic cycle, is initiated by Ni(0). Both paths require the presence of a catalytic amount of KOBu ^t . The results of the DFT studies presented here indicate that the rate-determining step in the initial Ni(II) system involves a concerted metalation-deprotonation (CMD) mechanism and an anionic Ni(0) ate complex is the key intermediate in the main catalytic cycle. Furthermore, a previously proposed oxidative addition-alkyne insertion sequence is revised to a ligand-to-ligand hydrogen transfer (LLHT) mechanism, which is the rate-determining step in the main catalytic cycle. The computed regioselectivity of the asymmetrical alkynes and meta-substituted aromatic amides that are produced in such reactions is in good agreement with the experimental results.