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Catalytic enantioselective addition of organometallics to unprotected carboxylic acids
Conjugate addition of organometallics to carbonyl based Michael acceptors is a widely used method that allows the building of new carbon-carbon (C-C) bonds and the introduction of chirality in a single step. However, conjugate additions to the simplest Michael acceptors, namely unprotected, unsatura...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667444/ https://www.ncbi.nlm.nih.gov/pubmed/31363092 http://dx.doi.org/10.1038/s41467-019-11345-z |
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author | Yan, Xingchen Harutyunyan, Syuzanna R. |
author_facet | Yan, Xingchen Harutyunyan, Syuzanna R. |
author_sort | Yan, Xingchen |
collection | PubMed |
description | Conjugate addition of organometallics to carbonyl based Michael acceptors is a widely used method that allows the building of new carbon-carbon (C-C) bonds and the introduction of chirality in a single step. However, conjugate additions to the simplest Michael acceptors, namely unprotected, unsaturated carboxylic acids, are considered to be prohibited by the fact that acid-base reactions overpower any other type of reactivity, including nucleophilic addition. Here we describe a transient protecting group strategy that allows efficient catalytic asymmetric additions of organomagnesium reagents to unprotected α,β-unsaturated carboxylic acids. This unorthodox pathway is achieved by preventing the formation of unreactive carboxylate salts by means of a reactive intermediate, allowing modifications of the carbon chain to proceed unhindered, while the stereochemistry is controlled with a chiral copper catalyst. A wide variety of β-chiral carboxylic acids, obtained with excellent enantioselectivities and yields, can be further transformed into valuable molecules through for instance catalytic decarboxylative cross-coupling reactions. |
format | Online Article Text |
id | pubmed-6667444 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66674442019-08-01 Catalytic enantioselective addition of organometallics to unprotected carboxylic acids Yan, Xingchen Harutyunyan, Syuzanna R. Nat Commun Article Conjugate addition of organometallics to carbonyl based Michael acceptors is a widely used method that allows the building of new carbon-carbon (C-C) bonds and the introduction of chirality in a single step. However, conjugate additions to the simplest Michael acceptors, namely unprotected, unsaturated carboxylic acids, are considered to be prohibited by the fact that acid-base reactions overpower any other type of reactivity, including nucleophilic addition. Here we describe a transient protecting group strategy that allows efficient catalytic asymmetric additions of organomagnesium reagents to unprotected α,β-unsaturated carboxylic acids. This unorthodox pathway is achieved by preventing the formation of unreactive carboxylate salts by means of a reactive intermediate, allowing modifications of the carbon chain to proceed unhindered, while the stereochemistry is controlled with a chiral copper catalyst. A wide variety of β-chiral carboxylic acids, obtained with excellent enantioselectivities and yields, can be further transformed into valuable molecules through for instance catalytic decarboxylative cross-coupling reactions. Nature Publishing Group UK 2019-07-30 /pmc/articles/PMC6667444/ /pubmed/31363092 http://dx.doi.org/10.1038/s41467-019-11345-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Yan, Xingchen Harutyunyan, Syuzanna R. Catalytic enantioselective addition of organometallics to unprotected carboxylic acids |
title | Catalytic enantioselective addition of organometallics to unprotected carboxylic acids |
title_full | Catalytic enantioselective addition of organometallics to unprotected carboxylic acids |
title_fullStr | Catalytic enantioselective addition of organometallics to unprotected carboxylic acids |
title_full_unstemmed | Catalytic enantioselective addition of organometallics to unprotected carboxylic acids |
title_short | Catalytic enantioselective addition of organometallics to unprotected carboxylic acids |
title_sort | catalytic enantioselective addition of organometallics to unprotected carboxylic acids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667444/ https://www.ncbi.nlm.nih.gov/pubmed/31363092 http://dx.doi.org/10.1038/s41467-019-11345-z |
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