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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...

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Autores principales: Yan, Xingchen, Harutyunyan, Syuzanna R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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.
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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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