Mechanistic Characterization of (Xantphos)Ni(I)-Mediated Alkyl Bromide Activation: Oxidative Addition, Electron Transfer, or Halogen-Atom Abstraction

Ni­(I)-mediated single-electron
oxidative activation of alkyl halides
has been extensively proposed as a key step in Ni-catalyzed cross-coupling
reactions to generate radical intermediates. There are four mechanisms
through which this step could take place: oxidative addition, outer-sphere
electron transfer, inner-sphere electron transfer, and concerted halogen-atom
abstraction. Despite considerable computational studies, there is
no experimental study to evaluate all four pathways for Ni­(I)-mediated
alkyl radical formation. Herein, we report the isolation of a series
of (Xantphos)­Ni­(I)–Ar complexes that selectively activate alkyl
halides over aryl halides to eject radicals and form Ni­(II) complexes.
This observation allows the application of kinetic studies on the
steric, electronic, and solvent effects, in combination with DFT calculations,
to systematically assess the four possible pathways. Our data reveal
that (Xantphos)­Ni­(I)-mediated alkyl halide activation proceeds via
a concerted halogen-atom abstraction mechanism. This result corroborates
previous DFT studies on (terpy)­Ni­(I)- and (py)­Ni­(I)-mediated alkyl
radical formation, and contrasts with the outer-sphere electron transfer
pathway observed for (PPh3)4Ni­(0)-mediated aryl
halide activation. This study of a model system provides insight
into the overall mechanism of Ni-catalyzed cross-coupling reactions
and offers a basis for differentiating electrophiles in cross-electrophile
coupling reactions.