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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...

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Autores principales: Ge, Luo, Sinnema, Esther G., Pérez, Juana M., Postolache, Roxana, Castiñeira Reis, Marta, Harutyunyan, Syuzanna R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
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.
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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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