Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp3)–N coupling
Abstract In drug development, the substitution of benzene rings in aniline-based drug candidates with saturated bridged bicyclic ring systems often enhances pharmacokinetic properties while preserving biological activity. However, current efforts predominantly focuses on bicyclo[1.1.1]pentylamines,...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54648-6 |
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| author | Kang-Ning Yuan Hongjun Zhuang Jie Wei Yu Shen Hong-Qing Yao Ming-Hong Li Lin-Lin Xu Ming Shang |
| author_facet | Kang-Ning Yuan Hongjun Zhuang Jie Wei Yu Shen Hong-Qing Yao Ming-Hong Li Lin-Lin Xu Ming Shang |
| author_sort | Kang-Ning Yuan |
| collection | DOAJ |
| description | Abstract In drug development, the substitution of benzene rings in aniline-based drug candidates with saturated bridged bicyclic ring systems often enhances pharmacokinetic properties while preserving biological activity. However, current efforts predominantly focuses on bicyclo[1.1.1]pentylamines, accessing analogs capable of mimicking ortho- and meta-substituted anilines remains challenging due to the lack of a versatile and modular synthetic methods. Herein, we present a modular approach to access a diverse array of saturated bioisosteres of anilines via photoelectrochemical-induced decarboxylative C(sp3)–N Coupling. The success of this reaction hinges on the merging the cooperative ligand-to-metal charge transfer (LMCT) with copper-catalyzed amination. Notably, this net-oxidative C(sp3)–N forming reaction operates under mild electrode potentials and proceeds through hydrogen evolution, eliminating the need for external chemical oxidants. Our research enables the facile decarboxylative amination of a set of sp3-rich small-ring cage carboxylic acids, thus offering a versatile bioisosteric replacement for ortho-, meta-, and para-substituted anilines and di(hetero)aryl amines. |
| format | Article |
| id | doaj-art-129ae9f9cef3422981a35e06ab5665d2 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-129ae9f9cef3422981a35e06ab5665d22025-01-26T12:41:56ZengNature PortfolioNature Communications2041-17232025-01-011611910.1038/s41467-024-54648-6Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp3)–N couplingKang-Ning Yuan0Hongjun Zhuang1Jie Wei2Yu Shen3Hong-Qing Yao4Ming-Hong Li5Lin-Lin Xu6Ming Shang7Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong UniversityResearch Center for Translational Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen UniversityFrontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong UniversityFrontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong UniversityFrontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong UniversityFrontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong UniversityFrontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong UniversityFrontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong UniversityAbstract In drug development, the substitution of benzene rings in aniline-based drug candidates with saturated bridged bicyclic ring systems often enhances pharmacokinetic properties while preserving biological activity. However, current efforts predominantly focuses on bicyclo[1.1.1]pentylamines, accessing analogs capable of mimicking ortho- and meta-substituted anilines remains challenging due to the lack of a versatile and modular synthetic methods. Herein, we present a modular approach to access a diverse array of saturated bioisosteres of anilines via photoelectrochemical-induced decarboxylative C(sp3)–N Coupling. The success of this reaction hinges on the merging the cooperative ligand-to-metal charge transfer (LMCT) with copper-catalyzed amination. Notably, this net-oxidative C(sp3)–N forming reaction operates under mild electrode potentials and proceeds through hydrogen evolution, eliminating the need for external chemical oxidants. Our research enables the facile decarboxylative amination of a set of sp3-rich small-ring cage carboxylic acids, thus offering a versatile bioisosteric replacement for ortho-, meta-, and para-substituted anilines and di(hetero)aryl amines.https://doi.org/10.1038/s41467-024-54648-6 |
| spellingShingle | Kang-Ning Yuan Hongjun Zhuang Jie Wei Yu Shen Hong-Qing Yao Ming-Hong Li Lin-Lin Xu Ming Shang Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp3)–N coupling Nature Communications |
| title | Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp3)–N coupling |
| title_full | Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp3)–N coupling |
| title_fullStr | Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp3)–N coupling |
| title_full_unstemmed | Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp3)–N coupling |
| title_short | Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp3)–N coupling |
| title_sort | modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative c sp3 n coupling |
| url | https://doi.org/10.1038/s41467-024-54648-6 |
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