Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water
Despite the myriad of selective enzymatic reactions that occur in water, chemists have rarely capitalized on the unique properties of this medium to govern selectivity in reactions. Here we report detailed mechanistic investigations of a water-promoted reaction that displays high selectivity for wha...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2014
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| Online Access: | http://hdl.handle.net/1721.1/87996 https://orcid.org/0000-0002-8601-7799 |
| _version_ | 1811093758612078592 |
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| author | Byers, Jeffery A. Jamison, Timothy F. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Byers, Jeffery A. Jamison, Timothy F. |
| author_sort | Byers, Jeffery A. |
| collection | MIT |
| description | Despite the myriad of selective enzymatic reactions that occur in water, chemists have rarely capitalized on the unique properties of this medium to govern selectivity in reactions. Here we report detailed mechanistic investigations of a water-promoted reaction that displays high selectivity for what is generally a disfavored product. A combination of structural and kinetic data indicates not only that synergy between substrate and water suppresses undesired pathways but also that water promotes the desired pathway by stabilizing charge in the transition state, facilitating proton transfer, doubly activating the substrate for reaction, and perhaps most remarkably, reorganizing the substrate into a reactive conformation that leads to the observed product. This approach serves as an outline for a general strategy of exploiting solvent-solute interactions to achieve unusual reactivity in chemical reactions. These findings may also have implications in the biosynthesis of the ladder polyether natural products, such as the brevetoxins and ciguatoxins. |
| first_indexed | 2024-09-23T15:50:12Z |
| format | Article |
| id | mit-1721.1/87996 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:50:12Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/879962022-09-29T16:26:29Z Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water Byers, Jeffery A. Jamison, Timothy F. Massachusetts Institute of Technology. Department of Chemistry Byers, Jeffery A. Jamison, Timothy F. Despite the myriad of selective enzymatic reactions that occur in water, chemists have rarely capitalized on the unique properties of this medium to govern selectivity in reactions. Here we report detailed mechanistic investigations of a water-promoted reaction that displays high selectivity for what is generally a disfavored product. A combination of structural and kinetic data indicates not only that synergy between substrate and water suppresses undesired pathways but also that water promotes the desired pathway by stabilizing charge in the transition state, facilitating proton transfer, doubly activating the substrate for reaction, and perhaps most remarkably, reorganizing the substrate into a reactive conformation that leads to the observed product. This approach serves as an outline for a general strategy of exploiting solvent-solute interactions to achieve unusual reactivity in chemical reactions. These findings may also have implications in the biosynthesis of the ladder polyether natural products, such as the brevetoxins and ciguatoxins. Petroleum Research Fund (47212-AC1) National Institute of General Medical Sciences (U.S.) (GM72566) 2014-06-16T14:53:17Z 2014-06-16T14:53:17Z 2013-09 2013-06 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/87996 Byers, J. A., and T. F. Jamison. “Entropic Factors Provide Unusual Reactivity and Selectivity in Epoxide-Opening Reactions Promoted by Water.” Proceedings of the National Academy of Sciences 110, no. 42 (October 15, 2013): 16724–16729. https://orcid.org/0000-0002-8601-7799 en_US http://dx.doi.org/10.1073/pnas.1311133110 Proceedings of the National Academy of Sciences 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 National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Byers, Jeffery A. Jamison, Timothy F. Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water |
| title | Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water |
| title_full | Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water |
| title_fullStr | Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water |
| title_full_unstemmed | Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water |
| title_short | Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water |
| title_sort | entropic factors provide unusual reactivity and selectivity in epoxide opening reactions promoted by water |
| url | http://hdl.handle.net/1721.1/87996 https://orcid.org/0000-0002-8601-7799 |
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