Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones: Access to Chiral 2‑Substituted Cyclopentyl Aryl Ketones
Asymmetric hydrogenation of tetrasubstituted alkenes is an important but challenging research topic. Herein, we report an efficient iridium-catalyzed asymmetric hydrogenation of tetrasubstituted α,β-unsaturated ketones for the synthesis of chiral 2-substituted cyclopentyl aryl ketones, an important...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Chemical Society
2023-02-01
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| Series: | Precision Chemistry |
| Online Access: | https://doi.org/10.1021/prechem.2c00010 |
| _version_ | 1797739856051306496 |
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| author | Zhengdong Ding Feng Gao Yining Lu Qianjia Yuan Wei-Ping Deng Wanbin Zhang |
| author_facet | Zhengdong Ding Feng Gao Yining Lu Qianjia Yuan Wei-Ping Deng Wanbin Zhang |
| author_sort | Zhengdong Ding |
| collection | DOAJ |
| description | Asymmetric hydrogenation of tetrasubstituted alkenes is an important but challenging research topic. Herein, we report an efficient iridium-catalyzed asymmetric hydrogenation of tetrasubstituted α,β-unsaturated ketones for the synthesis of chiral 2-substituted cyclopentyl aryl ketones, an important chiral structural motif for the preparation of chiral pharmaceuticals and bioactive molecules. The reaction proceeded very well with good functional group compatibility and delivered the hydrogenated products in high yields and stereoselectivities (up to 99% yield, >20:1 dr and 99% ee). In addition, the reaction could be carried out on a gram-scale, and all four stereoisomers of the hydrogenated products bearing two contiguous stereocenters were obtained. Furthermore, the hydrogenated product can be transformed into the ERβ agonist Erteberel, and the reaction pathway was also studied via deuterium-labelling experiments. |
| first_indexed | 2024-03-12T14:04:07Z |
| format | Article |
| id | doaj.art-d25b842e4d37442183bcd89c9953715f |
| institution | Directory Open Access Journal |
| issn | 2771-9316 |
| language | English |
| last_indexed | 2024-03-12T14:04:07Z |
| publishDate | 2023-02-01 |
| publisher | American Chemical Society |
| record_format | Article |
| series | Precision Chemistry |
| spelling | doaj.art-d25b842e4d37442183bcd89c9953715f2023-08-21T17:59:28ZengAmerican Chemical SocietyPrecision Chemistry2771-93162023-02-011314615210.1021/prechem.2c00010Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones: Access to Chiral 2‑Substituted Cyclopentyl Aryl KetonesZhengdong Ding0Feng Gao1Yining Lu2Qianjia Yuan3Wei-Ping Deng4Wanbin Zhang5Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, ChinaShanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaAsymmetric hydrogenation of tetrasubstituted alkenes is an important but challenging research topic. Herein, we report an efficient iridium-catalyzed asymmetric hydrogenation of tetrasubstituted α,β-unsaturated ketones for the synthesis of chiral 2-substituted cyclopentyl aryl ketones, an important chiral structural motif for the preparation of chiral pharmaceuticals and bioactive molecules. The reaction proceeded very well with good functional group compatibility and delivered the hydrogenated products in high yields and stereoselectivities (up to 99% yield, >20:1 dr and 99% ee). In addition, the reaction could be carried out on a gram-scale, and all four stereoisomers of the hydrogenated products bearing two contiguous stereocenters were obtained. Furthermore, the hydrogenated product can be transformed into the ERβ agonist Erteberel, and the reaction pathway was also studied via deuterium-labelling experiments.https://doi.org/10.1021/prechem.2c00010 |
| spellingShingle | Zhengdong Ding Feng Gao Yining Lu Qianjia Yuan Wei-Ping Deng Wanbin Zhang Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones: Access to Chiral 2‑Substituted Cyclopentyl Aryl Ketones Precision Chemistry |
| title | Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones: Access to Chiral 2‑Substituted Cyclopentyl Aryl Ketones |
| title_full | Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones: Access to Chiral 2‑Substituted Cyclopentyl Aryl Ketones |
| title_fullStr | Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones: Access to Chiral 2‑Substituted Cyclopentyl Aryl Ketones |
| title_full_unstemmed | Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones: Access to Chiral 2‑Substituted Cyclopentyl Aryl Ketones |
| title_short | Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones: Access to Chiral 2‑Substituted Cyclopentyl Aryl Ketones |
| title_sort | asymmetric hydrogenation of tetrasubstituted α β unsaturated ketones access to chiral 2 substituted cyclopentyl aryl ketones |
| url | https://doi.org/10.1021/prechem.2c00010 |
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