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

Abstract

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 analogous 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 precluding Lewis acid-base complexation between the Ni catalyst and the base, due to steric factors, is important for avoiding catalyst inhibition.

The Effect of Added Ligands on the Reactions of [Ni(COD)(dppf)] with Alkyl Halides: Halide Abstraction can be Reversible

“…For example, Liu et al found that [Ni(COD)2]/dppf was not a competent catalyst for the cross-coupling of phenyl triflate and aniline, but that a modified ligand (1,1'-bis(di(3,5-trifluoromethylphenyl)phosphino)ferrocene) enabled the reaction to achieve almost quantitative conversion. 6 There are many examples of situations where the mechanisms of nickel-catalysed reactions can also be very sensitive to ligand structure. If the nickel-catalysed Suzuki-Miyaura coupling of benzylic esters is carried out using tricyclohexylphosphine as the ligand the stereochemistry at the benzylic position is retained; however, the use of SIMes produces the stereoinverted product via a different mechanistic pathway.…”