Mechanistic Study of the Nickel-Catalyzed α,β-Coupling of Saturated Ketones

A combined
computational and experimental study of the mechanism
of a nickel-catalyzed α,β-coupling of saturated ketones
in the presence of an alkenyl halide is reported. The favored reaction
mechanism, as determined using DFT calculations, differs from the
previously proposed one and involves oxidative addition, transmetalation,
and a direct β-H transfer from the ketone to the alkenyl group.
The β-H transfer leads to a Ni-enone complex, reminiscent of
a Saegusa oxidation, followed by a Michael addition to generate the
final product. The β-H transfer is the rate-determining step
for the enone complex formation involving either a Ni–C species,
with an enolate C-bound to Ni, or a Ni–O species, with an enolate
O-bound to Ni. The Ni–C species β-H transfer follows
a more favorable, lower energy pathway. Experimental studies confirmed
the Ni-enone species to be an intermediate in the reaction pathway
and suggest that the enone dissociates from Ni before the final Michael
reaction with a lithium enolate to give the α,β-coupling
product. The mechanism also rationalizes the selectivity between the
previously reported enolate alkenylation and the presently studied
α,β-coupling reactions in the presence of PPh3 as a ligand. The alkenylation pathway with a PPh3 ligand
is calculated to be 5.8 kcal/mol higher in free energy of activation
than that of the ketone coupling pathway, which is consistent with
the experimental observation that no alkenylation products are formed
when the reaction was performed under α,β-coupling reaction
conditions.