Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study
We report the efficient N-arylation of acyclic secondary amides and related nucleophiles with aryl nonaflates, triflates, and chlorides. This method allows for easy variation of the aromatic component in tertiary aryl amides. A new biaryl phosphine with P-bound 3,5-(bis)trifluoromethylphenyl groups...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2012
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| Online Access: | http://hdl.handle.net/1721.1/71961 https://orcid.org/0000-0003-3875-4775 |
| _version_ | 1826209543275675648 |
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| author | Buchwald, Stephen Leffler Cuezva, Alberto Martinez Hicks, Jacqueline D. Hide, Alan M. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Buchwald, Stephen Leffler Cuezva, Alberto Martinez Hicks, Jacqueline D. Hide, Alan M. |
| author_sort | Buchwald, Stephen Leffler |
| collection | MIT |
| description | We report the efficient N-arylation of acyclic secondary amides and related nucleophiles with aryl nonaflates, triflates, and chlorides. This method allows for easy variation of the aromatic component in tertiary aryl amides. A new biaryl phosphine with P-bound 3,5-(bis)trifluoromethylphenyl groups was found to be uniquely effective for this amidation. The critical aspects of the ligand were explored through synthetic, mechanistic, and computational studies. Systematic variation of the ligand revealed the importance of (1) a methoxy group on the aromatic carbon of the “top ring” ortho to the phosphorus and (2) two highly electron-withdrawing P-bound 3,5-(bis)trifluoromethylphenyl groups. Computational studies suggest the electron-deficient nature of the ligand is important in facilitating amide binding to the LPd(II)(Ph)(X) intermediate. |
| first_indexed | 2024-09-23T14:24:08Z |
| format | Article |
| id | mit-1721.1/71961 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:24:08Z |
| publishDate | 2012 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/719612022-10-01T21:04:56Z Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study Buchwald, Stephen Leffler Cuezva, Alberto Martinez Hicks, Jacqueline D. Hide, Alan M. Massachusetts Institute of Technology. Department of Chemistry Buchwald, Stephen L. Buchwald, Stephen Leffler Cuezva, Alberto Martinez Hicks, Jacqueline D. Hyde, Alan M. We report the efficient N-arylation of acyclic secondary amides and related nucleophiles with aryl nonaflates, triflates, and chlorides. This method allows for easy variation of the aromatic component in tertiary aryl amides. A new biaryl phosphine with P-bound 3,5-(bis)trifluoromethylphenyl groups was found to be uniquely effective for this amidation. The critical aspects of the ligand were explored through synthetic, mechanistic, and computational studies. Systematic variation of the ligand revealed the importance of (1) a methoxy group on the aromatic carbon of the “top ring” ortho to the phosphorus and (2) two highly electron-withdrawing P-bound 3,5-(bis)trifluoromethylphenyl groups. Computational studies suggest the electron-deficient nature of the ligand is important in facilitating amide binding to the LPd(II)(Ph)(X) intermediate. National Institutes of Health (U.S.) (grant no. GM-58160) 2012-08-02T18:47:51Z 2012-08-02T18:47:51Z 2009-11 2009-06 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/71961 Buchwald, Stephen Leffler, et al. "Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study." Journal of the American Chemical Society 131.46 (2009): 16720-16734. https://orcid.org/0000-0003-3875-4775 en_US http://dx.doi.org/10.1021/ja9044357 Journal of the American Chemical Society Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Buchwald, Stephen Leffler Cuezva, Alberto Martinez Hicks, Jacqueline D. Hide, Alan M. Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study |
| title | Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study |
| title_full | Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study |
| title_fullStr | Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study |
| title_full_unstemmed | Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study |
| title_short | Pd-Catalyzed N-Arylation of Secondary Acyclic Amides: Catalyst Development, Scope, and Computational Study |
| title_sort | pd catalyzed n arylation of secondary acyclic amides catalyst development scope and computational study |
| url | http://hdl.handle.net/1721.1/71961 https://orcid.org/0000-0003-3875-4775 |
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