Copper‐Catalyzed Regio‐ and Enantioselective Hydroboration of Difluoroalkyl‐Substituted Internal Alkenes
Abstract Catalytic asymmetric hydroboration of fluoroalkyl‐substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl‐substituted alkenes without fluorine elimination has been a l...
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| Format: | Article |
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Wiley
2023-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202304194 |
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| author | Tao‐Qian Zhao Hui Xu Yu‐Chen Tian Xiaodong Tang Yanfeng Dang Shaozhong Ge Jun‐An Ma Fa‐Guang Zhang |
| author_facet | Tao‐Qian Zhao Hui Xu Yu‐Chen Tian Xiaodong Tang Yanfeng Dang Shaozhong Ge Jun‐An Ma Fa‐Guang Zhang |
| author_sort | Tao‐Qian Zhao |
| collection | DOAJ |
| description | Abstract Catalytic asymmetric hydroboration of fluoroalkyl‐substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl‐substituted alkenes without fluorine elimination has been a long‐standing challenge in this field. Herein, a copper‐catalyzed hydroboration of difluoroalkyl‐substituted internal alkenes with high levels of regio‐ and enantioselectivities is reported. The native carbonyl directing group, copper hydride system, and bisphosphine ligand play crucial roles in suppressing the undesired fluoride elimination. This atom‐economic protocol provides a practical synthetic platform to obtain a wide scope of enantioenriched secondary boronates bearing the difluoromethylene moieties under mild conditions. Synthetic applications including functionalization of biorelevant molecules, versatile functional group interconversions, and preparation of difluoroalkylated Terfenadine derivative are also demonstrated. |
| first_indexed | 2024-03-08T22:58:56Z |
| format | Article |
| id | doaj.art-d369991b1e8846b19d2254d0014f9134 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-08T22:58:56Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj.art-d369991b1e8846b19d2254d0014f91342023-12-16T04:16:14ZengWileyAdvanced Science2198-38442023-12-011035n/an/a10.1002/advs.202304194Copper‐Catalyzed Regio‐ and Enantioselective Hydroboration of Difluoroalkyl‐Substituted Internal AlkenesTao‐Qian Zhao0Hui Xu1Yu‐Chen Tian2Xiaodong Tang3Yanfeng Dang4Shaozhong Ge5Jun‐An Ma6Fa‐Guang Zhang7Joint School of National University of Singapore and Tianjin University International Campus of Tianjin University Binhai New City Fuzhou 350207 P. R. ChinaDepartment of Chemistry Tianjin Key Laboratory of Molecular Optoelectronic Sciences Frontiers Science Center for Synthetic Biology (Ministry of Education) Tianjin University Tianjin 300072 P. R. ChinaJoint School of National University of Singapore and Tianjin University International Campus of Tianjin University Binhai New City Fuzhou 350207 P. R. ChinaJoint School of National University of Singapore and Tianjin University International Campus of Tianjin University Binhai New City Fuzhou 350207 P. R. ChinaDepartment of Chemistry Tianjin Key Laboratory of Molecular Optoelectronic Sciences Frontiers Science Center for Synthetic Biology (Ministry of Education) Tianjin University Tianjin 300072 P. R. ChinaDepartment of Chemistry National University of Singapore 3 Science Drive 3 Singapore 117543 SingaporeJoint School of National University of Singapore and Tianjin University International Campus of Tianjin University Binhai New City Fuzhou 350207 P. R. ChinaDepartment of Chemistry Tianjin Key Laboratory of Molecular Optoelectronic Sciences Frontiers Science Center for Synthetic Biology (Ministry of Education) Tianjin University Tianjin 300072 P. R. ChinaAbstract Catalytic asymmetric hydroboration of fluoroalkyl‐substituted alkenes is a straightforward approach to access chiral small molecules possessing both fluorine and boron atoms. However, enantioselective hydroboration of fluoroalkyl‐substituted alkenes without fluorine elimination has been a long‐standing challenge in this field. Herein, a copper‐catalyzed hydroboration of difluoroalkyl‐substituted internal alkenes with high levels of regio‐ and enantioselectivities is reported. The native carbonyl directing group, copper hydride system, and bisphosphine ligand play crucial roles in suppressing the undesired fluoride elimination. This atom‐economic protocol provides a practical synthetic platform to obtain a wide scope of enantioenriched secondary boronates bearing the difluoromethylene moieties under mild conditions. Synthetic applications including functionalization of biorelevant molecules, versatile functional group interconversions, and preparation of difluoroalkylated Terfenadine derivative are also demonstrated.https://doi.org/10.1002/advs.202304194copper catalysisdifluoromethylene groupenantioselectivityhydroborationregioselectivity |
| spellingShingle | Tao‐Qian Zhao Hui Xu Yu‐Chen Tian Xiaodong Tang Yanfeng Dang Shaozhong Ge Jun‐An Ma Fa‐Guang Zhang Copper‐Catalyzed Regio‐ and Enantioselective Hydroboration of Difluoroalkyl‐Substituted Internal Alkenes Advanced Science copper catalysis difluoromethylene group enantioselectivity hydroboration regioselectivity |
| title | Copper‐Catalyzed Regio‐ and Enantioselective Hydroboration of Difluoroalkyl‐Substituted Internal Alkenes |
| title_full | Copper‐Catalyzed Regio‐ and Enantioselective Hydroboration of Difluoroalkyl‐Substituted Internal Alkenes |
| title_fullStr | Copper‐Catalyzed Regio‐ and Enantioselective Hydroboration of Difluoroalkyl‐Substituted Internal Alkenes |
| title_full_unstemmed | Copper‐Catalyzed Regio‐ and Enantioselective Hydroboration of Difluoroalkyl‐Substituted Internal Alkenes |
| title_short | Copper‐Catalyzed Regio‐ and Enantioselective Hydroboration of Difluoroalkyl‐Substituted Internal Alkenes |
| title_sort | copper catalyzed regio and enantioselective hydroboration of difluoroalkyl substituted internal alkenes |
| topic | copper catalysis difluoromethylene group enantioselectivity hydroboration regioselectivity |
| url | https://doi.org/10.1002/advs.202304194 |
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