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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...

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Autores principales: Lavernhe, Rémi, Torres‐Ochoa, Rubén O., Wang, Qian, Zhu, Jieping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
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.
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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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