Understanding Rate Acceleration and Stereoinduction of an Asymmetric Giese Reaction Mediated by a Chiral Rhodium Catalyst

The surprising acceleration of the addition of electron-rich radicals to α,β-unsaturated 2-acyl imidazoles by a chiral-at-metal rhodium catalyst is investigated. M06/Lanl2DZ (Rh),6-31G­(d) calculations reproduce the observed rate acceleration and shed light on a catalyst design where a rigid chiral pocket with a steric interaction >5 Å from the chiral metal center leads to the observed high stereoinduction. Analysis of the molecular orbitals of two key addition transition states emphasize the role of the catalyst as a Lewis acid without significant charge transfer

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