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 KOBut. 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.