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

preprint
submitted on 13.01.2020 and posted on 17.01.2020 by Richard Liu, Joseph Dennis, Stephen L. Buchwald
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.

Funding

Metal-Catalyzed Methods for Organic Synthesis

National Institute of General Medical Sciences

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History

Email Address of Submitting Author

ryl@mit.edu

Institution

Massachusetts Institute of Technology

Country

USA

ORCID For Submitting Author

0000-0003-0951-6487

Declaration of Conflict of Interest

None

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