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Copper‐Catalyzed Aza‐Sonogashira Cross‐Coupling To Form Ynimines: Development and Application to the Synthesis of Heterocycles
Nitrogen‐substituted alkynes, such as ynamines and ynamides, are versatile synthetic building blocks. Ynimines bearing additional nucleophilic and electrophilic centers relative to ynamines and ynamides are expected to have high synthetic potential. However, their chemical reactivity remains unexplo...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596870/ https://www.ncbi.nlm.nih.gov/pubmed/34469033 http://dx.doi.org/10.1002/anie.202110901 |
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author | Lavernhe, Rémi Torres‐Ochoa, Rubén O. Wang, Qian Zhu, Jieping |
author_facet | Lavernhe, Rémi Torres‐Ochoa, Rubén O. Wang, Qian Zhu, Jieping |
author_sort | Lavernhe, Rémi |
collection | PubMed |
description | Nitrogen‐substituted alkynes, such as ynamines and ynamides, are versatile synthetic building blocks. Ynimines bearing additional nucleophilic and electrophilic centers relative to ynamines and ynamides are expected to have high synthetic potential. However, their chemical reactivity remains unexplored owing mainly to the lack of synthetic accessibility. We report herein a versatile copper‐catalyzed synthesis of ynimines from readily available O‐acetyl ketoximes and terminal alkynes. A wide range of O‐acetyl ketoximes derived from diaryl ketones, aryl alkyl ketones and dialkyl ketones underwent cross‐coupling with a diverse set of terminal alkynes to afford the ynimines in good to excellent yields. An unprecedented [5+1] heteroannulation reaction exploiting the reactivity of the ynimine generated in situ was subsequently developed for the synthesis of medicinally important heterocycles, including isoquinolines, azaindoles, azabenzofurans, azabenzothiophenes and carbolines. |
format | Online Article Text |
id | pubmed-8596870 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85968702021-11-22 Copper‐Catalyzed Aza‐Sonogashira Cross‐Coupling To Form Ynimines: Development and Application to the Synthesis of Heterocycles Lavernhe, Rémi Torres‐Ochoa, Rubén O. Wang, Qian Zhu, Jieping Angew Chem Int Ed Engl Communications Nitrogen‐substituted alkynes, such as ynamines and ynamides, are versatile synthetic building blocks. Ynimines bearing additional nucleophilic and electrophilic centers relative to ynamines and ynamides are expected to have high synthetic potential. However, their chemical reactivity remains unexplored owing mainly to the lack of synthetic accessibility. We report herein a versatile copper‐catalyzed synthesis of ynimines from readily available O‐acetyl ketoximes and terminal alkynes. A wide range of O‐acetyl ketoximes derived from diaryl ketones, aryl alkyl ketones and dialkyl ketones underwent cross‐coupling with a diverse set of terminal alkynes to afford the ynimines in good to excellent yields. An unprecedented [5+1] heteroannulation reaction exploiting the reactivity of the ynimine generated in situ was subsequently developed for the synthesis of medicinally important heterocycles, including isoquinolines, azaindoles, azabenzofurans, azabenzothiophenes and carbolines. John Wiley and Sons Inc. 2021-10-05 2021-11-02 /pmc/articles/PMC8596870/ /pubmed/34469033 http://dx.doi.org/10.1002/anie.202110901 Text en © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Communications Lavernhe, Rémi Torres‐Ochoa, Rubén O. Wang, Qian Zhu, Jieping Copper‐Catalyzed Aza‐Sonogashira Cross‐Coupling To Form Ynimines: Development and Application to the Synthesis of Heterocycles |
title | Copper‐Catalyzed Aza‐Sonogashira Cross‐Coupling To Form Ynimines: Development and Application to the Synthesis of Heterocycles |
title_full | Copper‐Catalyzed Aza‐Sonogashira Cross‐Coupling To Form Ynimines: Development and Application to the Synthesis of Heterocycles |
title_fullStr | Copper‐Catalyzed Aza‐Sonogashira Cross‐Coupling To Form Ynimines: Development and Application to the Synthesis of Heterocycles |
title_full_unstemmed | Copper‐Catalyzed Aza‐Sonogashira Cross‐Coupling To Form Ynimines: Development and Application to the Synthesis of Heterocycles |
title_short | Copper‐Catalyzed Aza‐Sonogashira Cross‐Coupling To Form Ynimines: Development and Application to the Synthesis of Heterocycles |
title_sort | copper‐catalyzed aza‐sonogashira cross‐coupling to form ynimines: development and application to the synthesis of heterocycles |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596870/ https://www.ncbi.nlm.nih.gov/pubmed/34469033 http://dx.doi.org/10.1002/anie.202110901 |
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