Mechanistic Investigation of Enantioconvergent Kumada Reactions of Racemic α‑Bromoketones Catalyzed by a Nickel/Bis(oxazoline) Complex

In recent years,
a wide array of methods for achieving nickel-catalyzed
substitution reactions of alkyl electrophiles by organometallic nucleophiles,
including enantioconvergent processes, have been described; however,
experiment-focused mechanistic studies of such couplings have been
comparatively scarce. The most detailed mechanistic investigations
to date have examined catalysts that bear tridentate ligands and,
with one exception, processes that are not enantioselective; studies
of catalysts based on bidentate ligands could be anticipated to be
more challenging, due to difficulty in isolating proposed intermediates
as a result of instability arising from coordinative unsaturation.
In this investigation, we explore the mechanism of enantioconvergent
Kumada reactions of racemic α-bromoketones catalyzed by a nickel
complex that bears a bidentate chiral bis­(oxazoline) ligand. Utilizing
an array of mechanistic tools (including isolation and reactivity
studies of three of the four proposed nickel-containing intermediates,
as well as interrogation via EPR spectroscopy, UV–vis spectroscopy,
radical probes, and DFT calculations), we provide support for a pathway
in which carbon–carbon bond formation proceeds via a radical-chain
process wherein a nickel­(I) complex serves as the chain-carrying radical
and an organonickel­(II) complex is the predominant resting state of
the catalyst. Computations indicate that the coupling of this organonickel­(II)
complex with an organic radical is the stereochemistry-determining
step of the reaction.