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Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates
This study describes general methods for the enantioselective syntheses of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates through dirhodium tetracarboxylate-catalysed asymmetric cyclopropanation of vinyl heterocycles with aryl- or heteroaryldiazoacetat...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386643/ https://www.ncbi.nlm.nih.gov/pubmed/34522315 http://dx.doi.org/10.1039/d1sc02474d |
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author | Sharland, Jack C. Wei, Bo Hardee, David J. Hodges, Timothy R. Gong, Wei Voight, Eric A. Davies, Huw M. L. |
author_facet | Sharland, Jack C. Wei, Bo Hardee, David J. Hodges, Timothy R. Gong, Wei Voight, Eric A. Davies, Huw M. L. |
author_sort | Sharland, Jack C. |
collection | PubMed |
description | This study describes general methods for the enantioselective syntheses of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates through dirhodium tetracarboxylate-catalysed asymmetric cyclopropanation of vinyl heterocycles with aryl- or heteroaryldiazoacetates. The reactions are highly diastereoselective and high asymmetric induction could be achieved using either (R)-pantolactone as a chiral auxiliary or chiral dirhodium tetracarboxylate catalysts. For meta- or para-substituted aryl- or heteroaryldiazoacetates the optimum catalyst was Rh(2)(R-p-Ph-TPCP)(4). In the case of ortho-substituted aryl- or heteroaryldiazoacetates, the optimum catalyst was Rh(2)(R-TPPTTL)(4). For a highly enantioselective reaction with the ortho-substituted substrates, 2-chloropyridine was required as an additive in the presence of either 4 Å molecular sieves or 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Under the optimized conditions, the cyclopropanation could be conducted in the presence of a variety of heterocycles, such as pyridines, pyrazines, quinolines, indoles, oxadiazoles, thiophenes and pyrazoles. |
format | Online Article Text |
id | pubmed-8386643 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-83866432021-09-13 Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates Sharland, Jack C. Wei, Bo Hardee, David J. Hodges, Timothy R. Gong, Wei Voight, Eric A. Davies, Huw M. L. Chem Sci Chemistry This study describes general methods for the enantioselective syntheses of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates through dirhodium tetracarboxylate-catalysed asymmetric cyclopropanation of vinyl heterocycles with aryl- or heteroaryldiazoacetates. The reactions are highly diastereoselective and high asymmetric induction could be achieved using either (R)-pantolactone as a chiral auxiliary or chiral dirhodium tetracarboxylate catalysts. For meta- or para-substituted aryl- or heteroaryldiazoacetates the optimum catalyst was Rh(2)(R-p-Ph-TPCP)(4). In the case of ortho-substituted aryl- or heteroaryldiazoacetates, the optimum catalyst was Rh(2)(R-TPPTTL)(4). For a highly enantioselective reaction with the ortho-substituted substrates, 2-chloropyridine was required as an additive in the presence of either 4 Å molecular sieves or 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Under the optimized conditions, the cyclopropanation could be conducted in the presence of a variety of heterocycles, such as pyridines, pyrazines, quinolines, indoles, oxadiazoles, thiophenes and pyrazoles. The Royal Society of Chemistry 2021-07-27 /pmc/articles/PMC8386643/ /pubmed/34522315 http://dx.doi.org/10.1039/d1sc02474d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Sharland, Jack C. Wei, Bo Hardee, David J. Hodges, Timothy R. Gong, Wei Voight, Eric A. Davies, Huw M. L. Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates |
title | Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates |
title_full | Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates |
title_fullStr | Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates |
title_full_unstemmed | Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates |
title_short | Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates |
title_sort | asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386643/ https://www.ncbi.nlm.nih.gov/pubmed/34522315 http://dx.doi.org/10.1039/d1sc02474d |
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