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Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation
Substituted seven-membered N-heterocycles are prevalent bioactive epitopes and useful synthons for preparing enzyme inhibitors or molecular recognition systems. To fully exploit the chemical properties of this flexible N-heterocycle scaffold, efficient methods for its diverse functionalization are r...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150284/ https://www.ncbi.nlm.nih.gov/pubmed/29088108 http://dx.doi.org/10.3390/molecules22111871 |
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author | Spedding, Harold Karuso, Peter Liu, Fei |
author_facet | Spedding, Harold Karuso, Peter Liu, Fei |
author_sort | Spedding, Harold |
collection | PubMed |
description | Substituted seven-membered N-heterocycles are prevalent bioactive epitopes and useful synthons for preparing enzyme inhibitors or molecular recognition systems. To fully exploit the chemical properties of this flexible N-heterocycle scaffold, efficient methods for its diverse functionalization are required. Here we utilize the late-stage oxidation of tetrahydroazepines as an approach to access densely functionalized oxo-azepines in a total of 8 steps and ~30% overall yield from commercially available starting materials. Hydroboration of tetrahydroazepines proceeded with diastereoselectivity in a substrate-dependent manner to yield regioisomeric azepanols before their oxidation to the corresponding oxo-azepines. Regioselectivity of the hydroboration step may be improved moderately by a rhodium catalyst, albeit with loss of conversion to a competing hydrogenation pathway. Overall our method allows efficient access to azepanols and oxo-azepines as versatile epitopes and synthons with a high degree of diastereoselectivity and moderate regioselectivity. |
format | Online Article Text |
id | pubmed-6150284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61502842018-11-13 Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation Spedding, Harold Karuso, Peter Liu, Fei Molecules Article Substituted seven-membered N-heterocycles are prevalent bioactive epitopes and useful synthons for preparing enzyme inhibitors or molecular recognition systems. To fully exploit the chemical properties of this flexible N-heterocycle scaffold, efficient methods for its diverse functionalization are required. Here we utilize the late-stage oxidation of tetrahydroazepines as an approach to access densely functionalized oxo-azepines in a total of 8 steps and ~30% overall yield from commercially available starting materials. Hydroboration of tetrahydroazepines proceeded with diastereoselectivity in a substrate-dependent manner to yield regioisomeric azepanols before their oxidation to the corresponding oxo-azepines. Regioselectivity of the hydroboration step may be improved moderately by a rhodium catalyst, albeit with loss of conversion to a competing hydrogenation pathway. Overall our method allows efficient access to azepanols and oxo-azepines as versatile epitopes and synthons with a high degree of diastereoselectivity and moderate regioselectivity. MDPI 2017-10-31 /pmc/articles/PMC6150284/ /pubmed/29088108 http://dx.doi.org/10.3390/molecules22111871 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Spedding, Harold Karuso, Peter Liu, Fei Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation |
title | Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation |
title_full | Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation |
title_fullStr | Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation |
title_full_unstemmed | Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation |
title_short | Synthesis of Substituted Oxo-Azepines by Regio- and Diastereoselective Hydroxylation |
title_sort | synthesis of substituted oxo-azepines by regio- and diastereoselective hydroxylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150284/ https://www.ncbi.nlm.nih.gov/pubmed/29088108 http://dx.doi.org/10.3390/molecules22111871 |
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