Open AccessThe Quest for the Ideal Base: Rational Design of a Nickel Precatalyst Enables Mild, Homogeneous C–N Cross-Coupling
Author(s) -
Richard Y. Liu,
Joseph M. Dennis,
Stephen L. Buchwald
Publication year - 2020
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.0c00286
Subject(s) - chemistry , steric effects , triethylamine , aryl , catalysis , phosphine , denticity , nucleophile , amination , base (topology) , combinatorial chemistry , homogeneous catalysis , ligand (biochemistry) , palladium , amine gas treating , catalytic cycle , lewis acids and bases , coupling reaction , organic chemistry , crystal structure , mathematical analysis , mathematics , biochemistry , alkyl , receptor
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 p K a 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.