Evidence That Epoxide-Opening Cascades Promoted by Water Are Stepwise and Become Faster and More Selective After the First Cyclization
A detailed kinetic study of the endo-selective epoxide-opening cascade reaction of a diepoxy alcohol in neutral water was undertaken using 1H NMR spectroscopy. The observation of monoepoxide intermediates resulting from initial endo and exo cyclization indicated that the cascade proceeds via a stepw...
| Main Authors: | , , |
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2012
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| Online Access: | http://hdl.handle.net/1721.1/71971 https://orcid.org/0000-0002-8601-7799 |
| _version_ | 1811087432860303360 |
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| author | Morten, Christopher J. Byers, Jeffery A. Jamison, Timothy F. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Morten, Christopher J. Byers, Jeffery A. Jamison, Timothy F. |
| author_sort | Morten, Christopher J. |
| collection | MIT |
| description | A detailed kinetic study of the endo-selective epoxide-opening cascade reaction of a diepoxy alcohol in neutral water was undertaken using 1H NMR spectroscopy. The observation of monoepoxide intermediates resulting from initial endo and exo cyclization indicated that the cascade proceeds via a stepwise mechanism rather than through a concerted one. Independent synthesis and cyclization of these monoepoxide intermediates demonstrated that they are chemically and kinetically competent intermediates in the cascade. Analysis of each step of the reaction revealed that both the rate and regioselectivity of cyclization improve as the cascade reaction proceeds. In the second step, cyclization of an epoxy alcohol substrate templated by a fused diad of two tetrahydropyran rings proceeds with exceptionally high regioselectivity (endo:exo = 19:1), the highest we have measured in the opening of a simple trans-disubstituted epoxide. The origins of these observations are discussed. |
| first_indexed | 2024-09-23T13:46:00Z |
| format | Article |
| id | mit-1721.1/71971 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:46:00Z |
| publishDate | 2012 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/719712022-09-28T16:00:26Z Evidence That Epoxide-Opening Cascades Promoted by Water Are Stepwise and Become Faster and More Selective After the First Cyclization Morten, Christopher J. Byers, Jeffery A. Jamison, Timothy F. Massachusetts Institute of Technology. Department of Chemistry Jamison, Timothy F. Morten, Christopher J. Byers, Jeffery A. Jamison, Timothy F. A detailed kinetic study of the endo-selective epoxide-opening cascade reaction of a diepoxy alcohol in neutral water was undertaken using 1H NMR spectroscopy. The observation of monoepoxide intermediates resulting from initial endo and exo cyclization indicated that the cascade proceeds via a stepwise mechanism rather than through a concerted one. Independent synthesis and cyclization of these monoepoxide intermediates demonstrated that they are chemically and kinetically competent intermediates in the cascade. Analysis of each step of the reaction revealed that both the rate and regioselectivity of cyclization improve as the cascade reaction proceeds. In the second step, cyclization of an epoxy alcohol substrate templated by a fused diad of two tetrahydropyran rings proceeds with exceptionally high regioselectivity (endo:exo = 19:1), the highest we have measured in the opening of a simple trans-disubstituted epoxide. The origins of these observations are discussed. National Institute of General Medical Sciences (U.S.) (GM72566) Petroleum Research Fund (47212-AC1) 2012-08-03T13:25:32Z 2012-08-03T13:25:32Z 2011-01 2010-10 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/71971 Morten, Christopher J., Jeffery A. Byers, and Timothy F. Jamison. “Evidence That Epoxide-Opening Cascades Promoted by Water Are Stepwise and Become Faster and More Selective After the First Cyclization.” Journal of the American Chemical Society 133.6 (2011): 1902–1908. https://orcid.org/0000-0002-8601-7799 en_US http://dx.doi.org/10.1021/ja1088748 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 | Morten, Christopher J. Byers, Jeffery A. Jamison, Timothy F. Evidence That Epoxide-Opening Cascades Promoted by Water Are Stepwise and Become Faster and More Selective After the First Cyclization |
| title | Evidence That Epoxide-Opening Cascades Promoted by Water Are Stepwise and Become Faster and More Selective After the First Cyclization |
| title_full | Evidence That Epoxide-Opening Cascades Promoted by Water Are Stepwise and Become Faster and More Selective After the First Cyclization |
| title_fullStr | Evidence That Epoxide-Opening Cascades Promoted by Water Are Stepwise and Become Faster and More Selective After the First Cyclization |
| title_full_unstemmed | Evidence That Epoxide-Opening Cascades Promoted by Water Are Stepwise and Become Faster and More Selective After the First Cyclization |
| title_short | Evidence That Epoxide-Opening Cascades Promoted by Water Are Stepwise and Become Faster and More Selective After the First Cyclization |
| title_sort | evidence that epoxide opening cascades promoted by water are stepwise and become faster and more selective after the first cyclization |
| url | http://hdl.handle.net/1721.1/71971 https://orcid.org/0000-0002-8601-7799 |
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