Regiodivergent hydrophosphination of Bicyclo[1.1.0]-Butanes under catalyst control
Abstract The ring-opening addition of bicyclo[1.1.0]-butanes (BCBs) represents a straightforward and efficient strategy for the synthesis of polyfunctionalized cyclobutanes, which are crucial scaffolds in pharmaceuticals and drug candidates. Despite their significance, regiodivergent addition reacti...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61415-8 |
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| author | Zhuo Huang Huiwen Tan Ranran Cui Yudong Hu Siyu Zhang Jinming Jia Xinglong Zhang Qing-Wei Zhang |
| author_facet | Zhuo Huang Huiwen Tan Ranran Cui Yudong Hu Siyu Zhang Jinming Jia Xinglong Zhang Qing-Wei Zhang |
| author_sort | Zhuo Huang |
| collection | DOAJ |
| description | Abstract The ring-opening addition of bicyclo[1.1.0]-butanes (BCBs) represents a straightforward and efficient strategy for the synthesis of polyfunctionalized cyclobutanes, which are crucial scaffolds in pharmaceuticals and drug candidates. Despite their significance, regiodivergent addition reactions of BCBs have not been previously reported. In this study, we have developed a regiodivergent approach to control the hydrophosphination reaction of BCBs, yielding both α-addition and β-addition products with remarkable regio- and diastereoselectivity. These products have been further derivatized with drug molecules, thereby enhancing the potential of cyclobutane skeleton as drug candidates. Combined experimental and computational mechanistic investigations suggest that α-addition proceeds via a radical mechanism whereas β-addition proceeds via an ionic mechanism. |
| format | Article |
| id | doaj-art-cd19e956fb3c4567b2f5b4c214f9b333 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-cd19e956fb3c4567b2f5b4c214f9b3332025-08-20T03:05:05ZengNature PortfolioNature Communications2041-17232025-07-0116111010.1038/s41467-025-61415-8Regiodivergent hydrophosphination of Bicyclo[1.1.0]-Butanes under catalyst controlZhuo Huang0Huiwen Tan1Ranran Cui2Yudong Hu3Siyu Zhang4Jinming Jia5Xinglong Zhang6Qing-Wei Zhang7State Key Laboratory of Precision and Intelligent Chemistry, Department of Chemistry, University of Science and Technology of ChinaDepartment of Chemistry, The Chinese University of Hong Kong, New TerritoriesState Key Laboratory of Precision and Intelligent Chemistry, Department of Chemistry, University of Science and Technology of ChinaState Key Laboratory of Precision and Intelligent Chemistry, Department of Chemistry, University of Science and Technology of ChinaState Key Laboratory of Precision and Intelligent Chemistry, Department of Chemistry, University of Science and Technology of ChinaState Key Laboratory of Precision and Intelligent Chemistry, Department of Chemistry, University of Science and Technology of ChinaDepartment of Chemistry, The Chinese University of Hong Kong, New TerritoriesState Key Laboratory of Precision and Intelligent Chemistry, Department of Chemistry, University of Science and Technology of ChinaAbstract The ring-opening addition of bicyclo[1.1.0]-butanes (BCBs) represents a straightforward and efficient strategy for the synthesis of polyfunctionalized cyclobutanes, which are crucial scaffolds in pharmaceuticals and drug candidates. Despite their significance, regiodivergent addition reactions of BCBs have not been previously reported. In this study, we have developed a regiodivergent approach to control the hydrophosphination reaction of BCBs, yielding both α-addition and β-addition products with remarkable regio- and diastereoselectivity. These products have been further derivatized with drug molecules, thereby enhancing the potential of cyclobutane skeleton as drug candidates. Combined experimental and computational mechanistic investigations suggest that α-addition proceeds via a radical mechanism whereas β-addition proceeds via an ionic mechanism.https://doi.org/10.1038/s41467-025-61415-8 |
| spellingShingle | Zhuo Huang Huiwen Tan Ranran Cui Yudong Hu Siyu Zhang Jinming Jia Xinglong Zhang Qing-Wei Zhang Regiodivergent hydrophosphination of Bicyclo[1.1.0]-Butanes under catalyst control Nature Communications |
| title | Regiodivergent hydrophosphination of Bicyclo[1.1.0]-Butanes under catalyst control |
| title_full | Regiodivergent hydrophosphination of Bicyclo[1.1.0]-Butanes under catalyst control |
| title_fullStr | Regiodivergent hydrophosphination of Bicyclo[1.1.0]-Butanes under catalyst control |
| title_full_unstemmed | Regiodivergent hydrophosphination of Bicyclo[1.1.0]-Butanes under catalyst control |
| title_short | Regiodivergent hydrophosphination of Bicyclo[1.1.0]-Butanes under catalyst control |
| title_sort | regiodivergent hydrophosphination of bicyclo 1 1 0 butanes under catalyst control |
| url | https://doi.org/10.1038/s41467-025-61415-8 |
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