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Three-component radical homo Mannich reaction
Aliphatic amine, especially tertiary aliphatic amine, is one of the most popular functionalities found in pharmaceutical agents. The Mannich reaction is a classical and widely used transformation for the synthesis of β-amino-carbonyl products. Due to an ionic nature of the mechanism, the Mannich rea...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880990/ https://www.ncbi.nlm.nih.gov/pubmed/33579948 http://dx.doi.org/10.1038/s41467-021-21303-3 |
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author | Shi, Shuai Qiu, Wenting Miao, Pannan Li, Ruining Lin, Xianfeng Sun, Zhankui |
author_facet | Shi, Shuai Qiu, Wenting Miao, Pannan Li, Ruining Lin, Xianfeng Sun, Zhankui |
author_sort | Shi, Shuai |
collection | PubMed |
description | Aliphatic amine, especially tertiary aliphatic amine, is one of the most popular functionalities found in pharmaceutical agents. The Mannich reaction is a classical and widely used transformation for the synthesis of β-amino-carbonyl products. Due to an ionic nature of the mechanism, the Mannich reaction can only use non-enolizable aldehydes as substrates, which significantly limits the further applications of this powerful approach. Here we show, by employing a radical process, we are able to utilize enolizable aldehydes as substrates and develop the three-component radical homo Mannich reaction for the streamlined synthesis of γ-amino-carbonyl compounds. The electrophilic radicals are generated from thiols via the desulfurization process facilitated by visible-light, and then add to the electron-rich double bonds of the in-situ formed enamines to provide the products in a single step. The broad scope, mild conditions, high functional group tolerance, and modularity of this metal-free approach for the synthesis of complex tertiary amine scaffolds will likely be of great utility to chemists in both academia and industry. |
format | Online Article Text |
id | pubmed-7880990 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78809902021-02-24 Three-component radical homo Mannich reaction Shi, Shuai Qiu, Wenting Miao, Pannan Li, Ruining Lin, Xianfeng Sun, Zhankui Nat Commun Article Aliphatic amine, especially tertiary aliphatic amine, is one of the most popular functionalities found in pharmaceutical agents. The Mannich reaction is a classical and widely used transformation for the synthesis of β-amino-carbonyl products. Due to an ionic nature of the mechanism, the Mannich reaction can only use non-enolizable aldehydes as substrates, which significantly limits the further applications of this powerful approach. Here we show, by employing a radical process, we are able to utilize enolizable aldehydes as substrates and develop the three-component radical homo Mannich reaction for the streamlined synthesis of γ-amino-carbonyl compounds. The electrophilic radicals are generated from thiols via the desulfurization process facilitated by visible-light, and then add to the electron-rich double bonds of the in-situ formed enamines to provide the products in a single step. The broad scope, mild conditions, high functional group tolerance, and modularity of this metal-free approach for the synthesis of complex tertiary amine scaffolds will likely be of great utility to chemists in both academia and industry. Nature Publishing Group UK 2021-02-12 /pmc/articles/PMC7880990/ /pubmed/33579948 http://dx.doi.org/10.1038/s41467-021-21303-3 Text en © The Author(s) 2021 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 Shi, Shuai Qiu, Wenting Miao, Pannan Li, Ruining Lin, Xianfeng Sun, Zhankui Three-component radical homo Mannich reaction |
title | Three-component radical homo Mannich reaction |
title_full | Three-component radical homo Mannich reaction |
title_fullStr | Three-component radical homo Mannich reaction |
title_full_unstemmed | Three-component radical homo Mannich reaction |
title_short | Three-component radical homo Mannich reaction |
title_sort | three-component radical homo mannich reaction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880990/ https://www.ncbi.nlm.nih.gov/pubmed/33579948 http://dx.doi.org/10.1038/s41467-021-21303-3 |
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