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Enantio- and Z-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center
Olefins are ubiquitous in biologically active molecules and frequently used as building blocks in chemical transformations. However, although many strategies exist for the synthesis of stereodefined E-olefines, their thermodynamically less stable Z counterparts are substantially more demanding, whil...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839328/ https://www.ncbi.nlm.nih.gov/pubmed/36638168 http://dx.doi.org/10.1126/sciadv.adf8742 |
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author | Ge, Luo Sinnema, Esther G. Pérez, Juana M. Postolache, Roxana Castiñeira Reis, Marta Harutyunyan, Syuzanna R. |
author_facet | Ge, Luo Sinnema, Esther G. Pérez, Juana M. Postolache, Roxana Castiñeira Reis, Marta Harutyunyan, Syuzanna R. |
author_sort | Ge, Luo |
collection | PubMed |
description | Olefins are ubiquitous in biologically active molecules and frequently used as building blocks in chemical transformations. However, although many strategies exist for the synthesis of stereodefined E-olefines, their thermodynamically less stable Z counterparts are substantially more demanding, while access to those bearing an allylic stereocenter with an adjacent reactive functionality remains unsolved altogether. Even the classic Wittig reaction, arguably the most versatile and widely used approach to construct Z-alkenes, falls short for the synthesis of these particularly challenging yet highly useful structural motives. Here, we report a general methodology for Z-selective synthesis of functionalized chiral alkenes that establishes readily available alkene-derived phosphines as an alternative to alkylating reagents in Wittig olefination, thus offering previously unidentified retrosynthetic disconnections for the formation of functionalized disubstituted alkenes. We demonstrate the potential of this method by structural diversification of several bioactive molecules. |
format | Online Article Text |
id | pubmed-9839328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-98393282023-01-24 Enantio- and Z-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center Ge, Luo Sinnema, Esther G. Pérez, Juana M. Postolache, Roxana Castiñeira Reis, Marta Harutyunyan, Syuzanna R. Sci Adv Physical and Materials Sciences Olefins are ubiquitous in biologically active molecules and frequently used as building blocks in chemical transformations. However, although many strategies exist for the synthesis of stereodefined E-olefines, their thermodynamically less stable Z counterparts are substantially more demanding, while access to those bearing an allylic stereocenter with an adjacent reactive functionality remains unsolved altogether. Even the classic Wittig reaction, arguably the most versatile and widely used approach to construct Z-alkenes, falls short for the synthesis of these particularly challenging yet highly useful structural motives. Here, we report a general methodology for Z-selective synthesis of functionalized chiral alkenes that establishes readily available alkene-derived phosphines as an alternative to alkylating reagents in Wittig olefination, thus offering previously unidentified retrosynthetic disconnections for the formation of functionalized disubstituted alkenes. We demonstrate the potential of this method by structural diversification of several bioactive molecules. American Association for the Advancement of Science 2023-01-13 /pmc/articles/PMC9839328/ /pubmed/36638168 http://dx.doi.org/10.1126/sciadv.adf8742 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Physical and Materials Sciences Ge, Luo Sinnema, Esther G. Pérez, Juana M. Postolache, Roxana Castiñeira Reis, Marta Harutyunyan, Syuzanna R. Enantio- and Z-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center |
title | Enantio- and Z-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center |
title_full | Enantio- and Z-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center |
title_fullStr | Enantio- and Z-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center |
title_full_unstemmed | Enantio- and Z-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center |
title_short | Enantio- and Z-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center |
title_sort | enantio- and z-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center |
topic | Physical and Materials Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839328/ https://www.ncbi.nlm.nih.gov/pubmed/36638168 http://dx.doi.org/10.1126/sciadv.adf8742 |
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