The Quest for the Ideal Base: Rational Design of a Nickel Precatalyst Enables Mild, Homogeneous C–N Cross-Coupling
© 2020 American Chemical Society. 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 tria...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Chemical Society (ACS)
2021
|
| Online Access: | https://hdl.handle.net/1721.1/132537 |
| _version_ | 1811097236140982272 |
|---|---|
| author | Liu, Richard Y Dennis, Joseph M Buchwald, Stephen L |
| author_facet | Liu, Richard Y Dennis, Joseph M Buchwald, Stephen L |
| author_sort | Liu, Richard Y |
| collection | MIT |
| description | © 2020 American Chemical Society. 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. |
| first_indexed | 2024-09-23T16:56:27Z |
| format | Article |
| id | mit-1721.1/132537 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:56:27Z |
| publishDate | 2021 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1325372021-09-21T03:02:46Z The Quest for the Ideal Base: Rational Design of a Nickel Precatalyst Enables Mild, Homogeneous C–N Cross-Coupling Liu, Richard Y Dennis, Joseph M Buchwald, Stephen L © 2020 American Chemical Society. 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. 2021-09-20T18:22:55Z 2021-09-20T18:22:55Z 2020-11-16T15:25:23Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/132537 en 10.1021/JACS.0C00286 Journal of the American Chemical Society Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Chemical Society (ACS) chemRxiv |
| spellingShingle | Liu, Richard Y Dennis, Joseph M Buchwald, Stephen L The Quest for the Ideal Base: Rational Design of a Nickel Precatalyst Enables Mild, Homogeneous C–N Cross-Coupling |
| title | The Quest for the Ideal Base: Rational Design of a Nickel Precatalyst Enables Mild, Homogeneous C–N Cross-Coupling |
| title_full | The Quest for the Ideal Base: Rational Design of a Nickel Precatalyst Enables Mild, Homogeneous C–N Cross-Coupling |
| title_fullStr | The Quest for the Ideal Base: Rational Design of a Nickel Precatalyst Enables Mild, Homogeneous C–N Cross-Coupling |
| title_full_unstemmed | The Quest for the Ideal Base: Rational Design of a Nickel Precatalyst Enables Mild, Homogeneous C–N Cross-Coupling |
| title_short | The Quest for the Ideal Base: Rational Design of a Nickel Precatalyst Enables Mild, Homogeneous C–N Cross-Coupling |
| title_sort | quest for the ideal base rational design of a nickel precatalyst enables mild homogeneous c n cross coupling |
| url | https://hdl.handle.net/1721.1/132537 |
| work_keys_str_mv | AT liurichardy thequestfortheidealbaserationaldesignofanickelprecatalystenablesmildhomogeneouscncrosscoupling AT dennisjosephm thequestfortheidealbaserationaldesignofanickelprecatalystenablesmildhomogeneouscncrosscoupling AT buchwaldstephenl thequestfortheidealbaserationaldesignofanickelprecatalystenablesmildhomogeneouscncrosscoupling AT liurichardy questfortheidealbaserationaldesignofanickelprecatalystenablesmildhomogeneouscncrosscoupling AT dennisjosephm questfortheidealbaserationaldesignofanickelprecatalystenablesmildhomogeneouscncrosscoupling AT buchwaldstephenl questfortheidealbaserationaldesignofanickelprecatalystenablesmildhomogeneouscncrosscoupling |