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

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posted on 11.01.2018, 00:00 by Xin Zhang, Brandon Tutkowski, Allen Oliver, Paul Helquist, Olaf Wiest
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.