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One step synthesis of unsymmetrical 1,3-disubstituted BCP ketones via nickel/photoredox-catalyzed [1.1.1]propellane multicomponent dicarbofunctionalization
Bicyclo[1.1.1]pentanes (BCPs), utilized as sp(3)-rich bioisosteres for tert-butyl- and aryl groups as well as internal alkynes, have gained considerable momentum in drug development programs. Although many elegant methods have been developed to access BCP amines and BCP aryls efficiently, the method...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Royal Society of Chemistry
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580470/ https://www.ncbi.nlm.nih.gov/pubmed/36320918 http://dx.doi.org/10.1039/d2sc05100a |
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author | Huang, Weichen Keess, Sebastian Molander, Gary A. |
author_facet | Huang, Weichen Keess, Sebastian Molander, Gary A. |
author_sort | Huang, Weichen |
collection | PubMed |
description | Bicyclo[1.1.1]pentanes (BCPs), utilized as sp(3)-rich bioisosteres for tert-butyl- and aryl groups as well as internal alkynes, have gained considerable momentum in drug development programs. Although many elegant methods have been developed to access BCP amines and BCP aryls efficiently, the methods used to construct BCP ketones directly are relatively underdeveloped. In particular, the preparation of unsymmetrical 1,3-disubstituted-BCP ketones remains challenging and still requires multiple chemical steps. Herein, a single-step, multi-component approach to versatile disubstituted BCP ketones via nickel/photoredox catalysis is reported. Importantly, installing a boron group at the carbon position adjacent to the BCP structure bypasses the limitation to tertiary BF(3)K coupling partners, thus expanding the scope of this paradigm. Further transformation of disubstituted-BCP ketones into a variety of other BCP derivatives demonstrates the synthetic value of this developed method. |
format | Online Article Text |
id | pubmed-9580470 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-95804702022-10-31 One step synthesis of unsymmetrical 1,3-disubstituted BCP ketones via nickel/photoredox-catalyzed [1.1.1]propellane multicomponent dicarbofunctionalization Huang, Weichen Keess, Sebastian Molander, Gary A. Chem Sci Chemistry Bicyclo[1.1.1]pentanes (BCPs), utilized as sp(3)-rich bioisosteres for tert-butyl- and aryl groups as well as internal alkynes, have gained considerable momentum in drug development programs. Although many elegant methods have been developed to access BCP amines and BCP aryls efficiently, the methods used to construct BCP ketones directly are relatively underdeveloped. In particular, the preparation of unsymmetrical 1,3-disubstituted-BCP ketones remains challenging and still requires multiple chemical steps. Herein, a single-step, multi-component approach to versatile disubstituted BCP ketones via nickel/photoredox catalysis is reported. Importantly, installing a boron group at the carbon position adjacent to the BCP structure bypasses the limitation to tertiary BF(3)K coupling partners, thus expanding the scope of this paradigm. Further transformation of disubstituted-BCP ketones into a variety of other BCP derivatives demonstrates the synthetic value of this developed method. The Royal Society of Chemistry 2022-10-03 /pmc/articles/PMC9580470/ /pubmed/36320918 http://dx.doi.org/10.1039/d2sc05100a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Huang, Weichen Keess, Sebastian Molander, Gary A. One step synthesis of unsymmetrical 1,3-disubstituted BCP ketones via nickel/photoredox-catalyzed [1.1.1]propellane multicomponent dicarbofunctionalization |
title | One step synthesis of unsymmetrical 1,3-disubstituted BCP ketones via nickel/photoredox-catalyzed [1.1.1]propellane multicomponent dicarbofunctionalization |
title_full | One step synthesis of unsymmetrical 1,3-disubstituted BCP ketones via nickel/photoredox-catalyzed [1.1.1]propellane multicomponent dicarbofunctionalization |
title_fullStr | One step synthesis of unsymmetrical 1,3-disubstituted BCP ketones via nickel/photoredox-catalyzed [1.1.1]propellane multicomponent dicarbofunctionalization |
title_full_unstemmed | One step synthesis of unsymmetrical 1,3-disubstituted BCP ketones via nickel/photoredox-catalyzed [1.1.1]propellane multicomponent dicarbofunctionalization |
title_short | One step synthesis of unsymmetrical 1,3-disubstituted BCP ketones via nickel/photoredox-catalyzed [1.1.1]propellane multicomponent dicarbofunctionalization |
title_sort | one step synthesis of unsymmetrical 1,3-disubstituted bcp ketones via nickel/photoredox-catalyzed [1.1.1]propellane multicomponent dicarbofunctionalization |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580470/ https://www.ncbi.nlm.nih.gov/pubmed/36320918 http://dx.doi.org/10.1039/d2sc05100a |
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