N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution
Abstract Planar-chiral cyclophanes have gained considerable concerns for drug discovery due to their unique conformational strain and 3D structure. However, the enantioselective synthesis of planar-chiral cyclophanes is a long-standing challenge for the synthetic community. We herein describe an N-h...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46376-8 |
| _version_ | 1797259173049663488 |
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| author | Jiayan Li Ziyang Dong Yang Chen Zhanhui Yang Xinen Yan Meng Wang Chenyang Li Changgui Zhao |
| author_facet | Jiayan Li Ziyang Dong Yang Chen Zhanhui Yang Xinen Yan Meng Wang Chenyang Li Changgui Zhao |
| author_sort | Jiayan Li |
| collection | DOAJ |
| description | Abstract Planar-chiral cyclophanes have gained considerable concerns for drug discovery due to their unique conformational strain and 3D structure. However, the enantioselective synthesis of planar-chiral cyclophanes is a long-standing challenge for the synthetic community. We herein describe an N-heterocyclic carbene (NHC)-catalyzed asymmetric construction of planar-chiral cyclophanes. This transformation occurs through a dynamic kinetic resolution (DKR) process to convert racemic substrates into planar-chiral macrocycle scaffolds in good to high yields with high to excellent enantioselectivities. The ansa chain length and aromatic ring substituent size is crucial to achieve the DKR approach. Controlled experiments and DFT calculations were performed to clarify the DKR process. |
| first_indexed | 2024-04-24T23:05:13Z |
| format | Article |
| id | doaj.art-b4e4ed1af65a48439cc3bd7c19b4b18b |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T23:05:13Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-b4e4ed1af65a48439cc3bd7c19b4b18b2024-03-17T12:32:03ZengNature PortfolioNature Communications2041-17232024-03-0115111110.1038/s41467-024-46376-8N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolutionJiayan Li0Ziyang Dong1Yang Chen2Zhanhui Yang3Xinen Yan4Meng Wang5Chenyang Li6Changgui Zhao7Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal UniversityKey Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal UniversityDepartment of Organic Chemistry, College of Chemistry, Beijing University of Chemical TechnologyDepartment of Organic Chemistry, College of Chemistry, Beijing University of Chemical TechnologyKey Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal UniversityKey Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal UniversityKey Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal UniversityKey Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal UniversityAbstract Planar-chiral cyclophanes have gained considerable concerns for drug discovery due to their unique conformational strain and 3D structure. However, the enantioselective synthesis of planar-chiral cyclophanes is a long-standing challenge for the synthetic community. We herein describe an N-heterocyclic carbene (NHC)-catalyzed asymmetric construction of planar-chiral cyclophanes. This transformation occurs through a dynamic kinetic resolution (DKR) process to convert racemic substrates into planar-chiral macrocycle scaffolds in good to high yields with high to excellent enantioselectivities. The ansa chain length and aromatic ring substituent size is crucial to achieve the DKR approach. Controlled experiments and DFT calculations were performed to clarify the DKR process.https://doi.org/10.1038/s41467-024-46376-8 |
| spellingShingle | Jiayan Li Ziyang Dong Yang Chen Zhanhui Yang Xinen Yan Meng Wang Chenyang Li Changgui Zhao N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution Nature Communications |
| title | N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution |
| title_full | N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution |
| title_fullStr | N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution |
| title_full_unstemmed | N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution |
| title_short | N-Heterocyclic carbene-catalyzed enantioselective synthesis of planar-chiral cyclophanes via dynamic kinetic resolution |
| title_sort | n heterocyclic carbene catalyzed enantioselective synthesis of planar chiral cyclophanes via dynamic kinetic resolution |
| url | https://doi.org/10.1038/s41467-024-46376-8 |
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