The reaction of N-heteroaromatic compounds, such as 2-aryl-pyrrole, benzimidazole, imidazole, indole, and pyrazole derivatives, with alkynes in the presence of a catalytic amount of a nickel complex results in C–H/N–H oxidative annulation.
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. 2017866506655). 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.
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