Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile
We show that a chiral copper hydride (CuH) complex catalyzes C-C bond-forming dearomatization of pyridines and pyridazines at room temperature. The catalytic reaction operates directly on free heterocycles and generates the nucleophiles in situ, eliminating the need for stoichiometric preactivation...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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American Chemical Society (ACS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/126089 |
| _version_ | 1811077481953755136 |
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| author | Gribble, Michael William Guo, Sheng Buchwald, Stephen Leffler |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Gribble, Michael William Guo, Sheng Buchwald, Stephen Leffler |
| author_sort | Gribble, Michael William |
| collection | MIT |
| description | We show that a chiral copper hydride (CuH) complex catalyzes C-C bond-forming dearomatization of pyridines and pyridazines at room temperature. The catalytic reaction operates directly on free heterocycles and generates the nucleophiles in situ, eliminating the need for stoichiometric preactivation of either reaction partner; further, it is one of very few methods available for the enantioselective 1,4-dearomatization of heteroarenes. Combining the dearomatization with facile derivatization steps enables one-pot syntheses of enantioenriched pyridines and piperidines. |
| first_indexed | 2024-09-23T10:43:43Z |
| format | Article |
| id | mit-1721.1/126089 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:43:43Z |
| publishDate | 2020 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1260892024-06-25T18:45:07Z Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile Gribble, Michael William Guo, Sheng Buchwald, Stephen Leffler Massachusetts Institute of Technology. Department of Chemistry We show that a chiral copper hydride (CuH) complex catalyzes C-C bond-forming dearomatization of pyridines and pyridazines at room temperature. The catalytic reaction operates directly on free heterocycles and generates the nucleophiles in situ, eliminating the need for stoichiometric preactivation of either reaction partner; further, it is one of very few methods available for the enantioselective 1,4-dearomatization of heteroarenes. Combining the dearomatization with facile derivatization steps enables one-pot syntheses of enantioenriched pyridines and piperidines. National Institutes of Health (award nos. GM46059 and R35-GM122483) 2020-07-08T19:06:22Z 2020-07-08T19:06:22Z 2018-04 2019-12-12T18:49:31Z Article http://purl.org/eprint/type/JournalArticle 1520-5126 https://hdl.handle.net/1721.1/126089 Gribble, Michael W., Jr., Sheng Guo, and Stephen L. Buchwald. "Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile." Journal of the American Chemical Society 140, 15 (Apr. 2018): p. 5057-60 doi 10.1021/JACS.8B02568 ©2018 Author(s) en 10.1021/JACS.8B02568 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 | Gribble, Michael William Guo, Sheng Buchwald, Stephen Leffler Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile |
| title | Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile |
| title_full | Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile |
| title_fullStr | Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile |
| title_full_unstemmed | Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile |
| title_short | Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile |
| title_sort | asymmetric cu catalyzed 1 4 dearomatization of pyridines and pyridazines without preactivation of the heterocycle or nucleophile |
| url | https://hdl.handle.net/1721.1/126089 |
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