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Nickel-catalyzed transamidation of aliphatic amide derivatives
Transamidation, or the conversion of one amide to another, is a long-standing challenge in organic synthesis. Although notable progress has been made in the transamidation of primary amides, the transamidation of secondary amides has remained underdeveloped, especially when considering aliphatic sub...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Royal Society of Chemistry
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632791/ https://www.ncbi.nlm.nih.gov/pubmed/29163929 http://dx.doi.org/10.1039/c7sc01980g |
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author | Dander, Jacob E. Baker, Emma L. Garg, Neil K. |
author_facet | Dander, Jacob E. Baker, Emma L. Garg, Neil K. |
author_sort | Dander, Jacob E. |
collection | PubMed |
description | Transamidation, or the conversion of one amide to another, is a long-standing challenge in organic synthesis. Although notable progress has been made in the transamidation of primary amides, the transamidation of secondary amides has remained underdeveloped, especially when considering aliphatic substrates. Herein, we report a two-step approach to achieve the transamidation of secondary aliphatic amides, which relies on non-precious metal catalysis. The method involves initial Boc-functionalization of secondary amide substrates to weaken the amide C–N bond. Subsequent treatment with a nickel catalyst, in the presence of an appropriate amine coupling partner, then delivers the net transamidated products. The transformation proceeds in synthetically useful yields across a range of substrates. A series of competition experiments delineate selectivity patterns that should influence future synthetic design. Moreover, the transamidation of Boc-activated secondary amide derivatives bearing epimerizable stereocenters underscores the mildness and synthetic utility of this methodology. This study provides the most general solution to the classic problem of secondary amide transamidation reported to date. |
format | Online Article Text |
id | pubmed-5632791 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-56327912017-11-21 Nickel-catalyzed transamidation of aliphatic amide derivatives Dander, Jacob E. Baker, Emma L. Garg, Neil K. Chem Sci Chemistry Transamidation, or the conversion of one amide to another, is a long-standing challenge in organic synthesis. Although notable progress has been made in the transamidation of primary amides, the transamidation of secondary amides has remained underdeveloped, especially when considering aliphatic substrates. Herein, we report a two-step approach to achieve the transamidation of secondary aliphatic amides, which relies on non-precious metal catalysis. The method involves initial Boc-functionalization of secondary amide substrates to weaken the amide C–N bond. Subsequent treatment with a nickel catalyst, in the presence of an appropriate amine coupling partner, then delivers the net transamidated products. The transformation proceeds in synthetically useful yields across a range of substrates. A series of competition experiments delineate selectivity patterns that should influence future synthetic design. Moreover, the transamidation of Boc-activated secondary amide derivatives bearing epimerizable stereocenters underscores the mildness and synthetic utility of this methodology. This study provides the most general solution to the classic problem of secondary amide transamidation reported to date. Royal Society of Chemistry 2017-09-01 2017-07-10 /pmc/articles/PMC5632791/ /pubmed/29163929 http://dx.doi.org/10.1039/c7sc01980g Text en This journal is © The Royal Society of Chemistry 2017 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0) |
spellingShingle | Chemistry Dander, Jacob E. Baker, Emma L. Garg, Neil K. Nickel-catalyzed transamidation of aliphatic amide derivatives |
title | Nickel-catalyzed transamidation of aliphatic amide derivatives
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title_full | Nickel-catalyzed transamidation of aliphatic amide derivatives
|
title_fullStr | Nickel-catalyzed transamidation of aliphatic amide derivatives
|
title_full_unstemmed | Nickel-catalyzed transamidation of aliphatic amide derivatives
|
title_short | Nickel-catalyzed transamidation of aliphatic amide derivatives
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title_sort | nickel-catalyzed transamidation of aliphatic amide derivatives |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632791/ https://www.ncbi.nlm.nih.gov/pubmed/29163929 http://dx.doi.org/10.1039/c7sc01980g |
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