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Iridium-catalyzed reductive Ugi-type reactions of tertiary amides

Amides are ubiquitous in the fine chemical, agrochemical and pharmaceutical industries, but are rarely exploited as substrates for homologous amine synthesis. By virtue of their high chemical stability, they are essentially inert to all but the harshest of chemical reagents and to the majority of ch...

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Autores principales: Xie, Lan-Gui, Dixon, Darren J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053461/
https://www.ncbi.nlm.nih.gov/pubmed/30026608
http://dx.doi.org/10.1038/s41467-018-05192-7
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author Xie, Lan-Gui
Dixon, Darren J.
author_facet Xie, Lan-Gui
Dixon, Darren J.
author_sort Xie, Lan-Gui
collection PubMed
description Amides are ubiquitous in the fine chemical, agrochemical and pharmaceutical industries, but are rarely exploited as substrates for homologous amine synthesis. By virtue of their high chemical stability, they are essentially inert to all but the harshest of chemical reagents and to the majority of chemical transformations routinely used in organic synthesis. Accordingly, the development of chemoselective carbon−carbon bond-forming methodologies arising from the functionalization of the amide functionality should find widespread use across academia and industry. We herein present our findings on a series of Ugi-type reactions of tertiary amides enabled by an initial chemoselective iridium-catalyzed partial reduction, followed by reaction with isocyanide and (thio)acetic acid or trimethylsilyl azide, thus providing a multicomponent synthesis of α-amino (thio)amide or α-amino tetrazole derivatives. The reductive Ugi-type reactions are amenable to a broad range of amides and isocyanides, and are applicable to late-stage functionalization of various bioactive molecules and pharmaceutical compounds.
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spelling pubmed-60534612018-07-25 Iridium-catalyzed reductive Ugi-type reactions of tertiary amides Xie, Lan-Gui Dixon, Darren J. Nat Commun Article Amides are ubiquitous in the fine chemical, agrochemical and pharmaceutical industries, but are rarely exploited as substrates for homologous amine synthesis. By virtue of their high chemical stability, they are essentially inert to all but the harshest of chemical reagents and to the majority of chemical transformations routinely used in organic synthesis. Accordingly, the development of chemoselective carbon−carbon bond-forming methodologies arising from the functionalization of the amide functionality should find widespread use across academia and industry. We herein present our findings on a series of Ugi-type reactions of tertiary amides enabled by an initial chemoselective iridium-catalyzed partial reduction, followed by reaction with isocyanide and (thio)acetic acid or trimethylsilyl azide, thus providing a multicomponent synthesis of α-amino (thio)amide or α-amino tetrazole derivatives. The reductive Ugi-type reactions are amenable to a broad range of amides and isocyanides, and are applicable to late-stage functionalization of various bioactive molecules and pharmaceutical compounds. Nature Publishing Group UK 2018-07-19 /pmc/articles/PMC6053461/ /pubmed/30026608 http://dx.doi.org/10.1038/s41467-018-05192-7 Text en © The Author(s) 2018 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
Xie, Lan-Gui
Dixon, Darren J.
Iridium-catalyzed reductive Ugi-type reactions of tertiary amides
title Iridium-catalyzed reductive Ugi-type reactions of tertiary amides
title_full Iridium-catalyzed reductive Ugi-type reactions of tertiary amides
title_fullStr Iridium-catalyzed reductive Ugi-type reactions of tertiary amides
title_full_unstemmed Iridium-catalyzed reductive Ugi-type reactions of tertiary amides
title_short Iridium-catalyzed reductive Ugi-type reactions of tertiary amides
title_sort iridium-catalyzed reductive ugi-type reactions of tertiary amides
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053461/
https://www.ncbi.nlm.nih.gov/pubmed/30026608
http://dx.doi.org/10.1038/s41467-018-05192-7
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