Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives
The identification and understanding of structure–activity relationships is vital for rational catalyst design. A kinetic study of the hydrogen–deuterium exchange reaction of cyclohexanone in aqueous solution, as catalyzed by proline derivatives, has revealed valuable structure–activity relationship...
| 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/1721.1/123680 |
| _version_ | 1826207522802892800 |
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| author | Myers, Eddie L. Palte, Michael J. Raines, Ronald T |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Myers, Eddie L. Palte, Michael J. Raines, Ronald T |
| author_sort | Myers, Eddie L. |
| collection | MIT |
| description | The identification and understanding of structure–activity relationships is vital for rational catalyst design. A kinetic study of the hydrogen–deuterium exchange reaction of cyclohexanone in aqueous solution, as catalyzed by proline derivatives, has revealed valuable structure–activity relationships. In phosphate-buffered solution, cis-4-fluoroproline is more active than the trans isomer, a distinction that appears to originate from a destabilizing interaction between the fluorine atom and phosphate anion during general acid-catalyzed dehydration of the carbinolamine intermediate. trans-4-Ammoniumprolines are exceptionally active catalysts owing to favorable Coulombic interactions involving the ammonium group and the alkoxide moiety formed upon 1,2-addition of the proline derivative to the ketone. These results could be used for the optimization of proline catalysts, especially in transformations where the formation of the putative iminium ion is rate-limiting. |
| first_indexed | 2024-09-23T13:50:52Z |
| format | Article |
| id | mit-1721.1/123680 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:50:52Z |
| publishDate | 2020 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1236802022-10-01T17:29:30Z Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives Myers, Eddie L. Palte, Michael J. Raines, Ronald T Massachusetts Institute of Technology. Department of Chemistry The identification and understanding of structure–activity relationships is vital for rational catalyst design. A kinetic study of the hydrogen–deuterium exchange reaction of cyclohexanone in aqueous solution, as catalyzed by proline derivatives, has revealed valuable structure–activity relationships. In phosphate-buffered solution, cis-4-fluoroproline is more active than the trans isomer, a distinction that appears to originate from a destabilizing interaction between the fluorine atom and phosphate anion during general acid-catalyzed dehydration of the carbinolamine intermediate. trans-4-Ammoniumprolines are exceptionally active catalysts owing to favorable Coulombic interactions involving the ammonium group and the alkoxide moiety formed upon 1,2-addition of the proline derivative to the ketone. These results could be used for the optimization of proline catalysts, especially in transformations where the formation of the putative iminium ion is rate-limiting. National Institutes of Health (U.S.). (Grant R01 AR044276) National Institutes of Health (U.S.). (Grant R01 GM04478) 2020-01-24T16:32:49Z 2020-01-24T16:32:49Z 2019-01 2018-10 2020-01-07T15:10:58Z Article http://purl.org/eprint/type/JournalArticle 0022-3263 1520-6904 https://hdl.handle.net/1721.1/123680 Myers, Eddie L. et al. "Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives." Journal of Organic Chemistry 84, 3 (January 2019): 1247-1256 © 2019 American Chemical Society en http://dx.doi.org/10.1021/acs.joc.8b02644 Journal of Organic Chemistry 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 | Myers, Eddie L. Palte, Michael J. Raines, Ronald T Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives |
| title | Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives |
| title_full | Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives |
| title_fullStr | Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives |
| title_full_unstemmed | Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives |
| title_short | Catalysis of Hydrogen–Deuterium Exchange Reactions by 4-Substituted Proline Derivatives |
| title_sort | catalysis of hydrogen deuterium exchange reactions by 4 substituted proline derivatives |
| url | https://hdl.handle.net/1721.1/123680 |
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