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Synthesis of Benzo[b]azocin‐2‐ones by Aryl Amination and Ring‐Expansion of α‐(Iodophenyl)‐β‐oxoesters
Transformation of β‐oxoesters with PhI(OCOCF(3))(2) leads to α‐(ortho‐iodophenyl)‐β‐oxoesters. These materials are the starting point for the synthesis of 6‐carboxybenzo[b]azocin‐2‐ones by a sequence of aryl amination and ring transformation. This reaction sequence starts with copper‐catalyzed forma...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899745/ https://www.ncbi.nlm.nih.gov/pubmed/31433088 http://dx.doi.org/10.1002/chem.201903139 |
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author | Dierks, Anna Tönjes, Jan Schmidtmann, Marc Christoffers, Jens |
author_facet | Dierks, Anna Tönjes, Jan Schmidtmann, Marc Christoffers, Jens |
author_sort | Dierks, Anna |
collection | PubMed |
description | Transformation of β‐oxoesters with PhI(OCOCF(3))(2) leads to α‐(ortho‐iodophenyl)‐β‐oxoesters. These materials are the starting point for the synthesis of 6‐carboxybenzo[b]azocin‐2‐ones by a sequence of aryl amination and ring transformation. This reaction sequence starts with copper‐catalyzed formation of N‐alkyl anilines from the iodoarenes and primary amines in the presence of K(3)PO(4) as stoichiometric base. The intermediate products underwent ring transformation by addition of the nitrogen into the carbonyl group of the cycloalkanone, furnishing benzo‐annulated eight‐membered ring lactams. Under the same reaction conditions, the cyclohexanone and cycloheptanone derivatives gave no aminated products, but ring‐transformed to benzofuran derivatives. The title compounds of this investigation contain two points for further diversification (the lactam nitrogen and the carboxylate function), thus, the suitability of this compound class as a scaffold was proven by appropriate functionalizations. The first series of derivatizations of the scaffold was initiated by hydrogenolytic debenzylation of N‐benzyl derivative to provide the NH‐congener, which could be deprotonated with LDA and alkylated at nitrogen to give further examples of this compound class. Secondly, the ester function was submitted to saponification and the resulting carboxylic acid could be amidated using HATU as coupling reagent to furnish different amides. |
format | Online Article Text |
id | pubmed-6899745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68997452019-12-19 Synthesis of Benzo[b]azocin‐2‐ones by Aryl Amination and Ring‐Expansion of α‐(Iodophenyl)‐β‐oxoesters Dierks, Anna Tönjes, Jan Schmidtmann, Marc Christoffers, Jens Chemistry Full Papers Transformation of β‐oxoesters with PhI(OCOCF(3))(2) leads to α‐(ortho‐iodophenyl)‐β‐oxoesters. These materials are the starting point for the synthesis of 6‐carboxybenzo[b]azocin‐2‐ones by a sequence of aryl amination and ring transformation. This reaction sequence starts with copper‐catalyzed formation of N‐alkyl anilines from the iodoarenes and primary amines in the presence of K(3)PO(4) as stoichiometric base. The intermediate products underwent ring transformation by addition of the nitrogen into the carbonyl group of the cycloalkanone, furnishing benzo‐annulated eight‐membered ring lactams. Under the same reaction conditions, the cyclohexanone and cycloheptanone derivatives gave no aminated products, but ring‐transformed to benzofuran derivatives. The title compounds of this investigation contain two points for further diversification (the lactam nitrogen and the carboxylate function), thus, the suitability of this compound class as a scaffold was proven by appropriate functionalizations. The first series of derivatizations of the scaffold was initiated by hydrogenolytic debenzylation of N‐benzyl derivative to provide the NH‐congener, which could be deprotonated with LDA and alkylated at nitrogen to give further examples of this compound class. Secondly, the ester function was submitted to saponification and the resulting carboxylic acid could be amidated using HATU as coupling reagent to furnish different amides. John Wiley and Sons Inc. 2019-10-28 2019-11-22 /pmc/articles/PMC6899745/ /pubmed/31433088 http://dx.doi.org/10.1002/chem.201903139 Text en © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full Papers Dierks, Anna Tönjes, Jan Schmidtmann, Marc Christoffers, Jens Synthesis of Benzo[b]azocin‐2‐ones by Aryl Amination and Ring‐Expansion of α‐(Iodophenyl)‐β‐oxoesters |
title | Synthesis of Benzo[b]azocin‐2‐ones by Aryl Amination and Ring‐Expansion of α‐(Iodophenyl)‐β‐oxoesters |
title_full | Synthesis of Benzo[b]azocin‐2‐ones by Aryl Amination and Ring‐Expansion of α‐(Iodophenyl)‐β‐oxoesters |
title_fullStr | Synthesis of Benzo[b]azocin‐2‐ones by Aryl Amination and Ring‐Expansion of α‐(Iodophenyl)‐β‐oxoesters |
title_full_unstemmed | Synthesis of Benzo[b]azocin‐2‐ones by Aryl Amination and Ring‐Expansion of α‐(Iodophenyl)‐β‐oxoesters |
title_short | Synthesis of Benzo[b]azocin‐2‐ones by Aryl Amination and Ring‐Expansion of α‐(Iodophenyl)‐β‐oxoesters |
title_sort | synthesis of benzo[b]azocin‐2‐ones by aryl amination and ring‐expansion of α‐(iodophenyl)‐β‐oxoesters |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899745/ https://www.ncbi.nlm.nih.gov/pubmed/31433088 http://dx.doi.org/10.1002/chem.201903139 |
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