The Quest for the Ideal Base: Rational Design of a Nickel Precatalyst Enables Mild, Homogeneous C–N Cross-Coupling

Palladium-catalyzed
amination reactions using soluble organic bases
have provided a solution to the many issues associated with heterogeneous
reaction conditions. Still, homogeneous C–N cross-coupling
approaches cannot yet employ bases as weak and economical as trialkyl­amines.
Furthermore, organic base-mediated methods have not been developed
for Ni­(0/II) catalysis, despite some advantages of such systems over
those employing Pd-based catalysts. We designed a new air-stable and
easily prepared Ni­(II) precatalyst bearing an electron-deficient bidentate
phosphine ligand that enables the cross-coupling of aryl triflates
with aryl amines using triethyl­amine (TEA) as base. The method
is tolerant of sterically congested coupling partners, as well as
those bearing base- and nucleophile-sensitive functional groups. With
the aid of density functional theory (DFT) calculations, we determined
that the electron-deficient auxiliary ligands decrease both the pKa of the Ni-bound amine and the barrier to reductive
elimination from the resultant Ni­(II)–amido complex. Moreover,
we determined that the preclusion of Lewis acid–base complexation
between the Ni catalyst and the base, due to steric factors, is important
for avoiding catalyst inhibition.