Expedient access to bora-butenolide bioisosteres by counteranion-mediated trans-hydroboration of alkynes
Abstract The hydroboration of alkynes is a textbook example of a syn-selective concerted addition reaction, while trans-selective additions of borane to alkynes remain to be developed. We herein report a transition metal-free anti-addition of pinacolborane to alkynes, facilitated by the counteranion...
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60052-5 |
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| author | Yuan-Wen Liu Yu Liu Yanting Zheng Mengfan Zhang Meng-En Ren Peiyu Hua Jie Han Alois Fürstner Hongming Jin |
| author_facet | Yuan-Wen Liu Yu Liu Yanting Zheng Mengfan Zhang Meng-En Ren Peiyu Hua Jie Han Alois Fürstner Hongming Jin |
| author_sort | Yuan-Wen Liu |
| collection | DOAJ |
| description | Abstract The hydroboration of alkynes is a textbook example of a syn-selective concerted addition reaction, while trans-selective additions of borane to alkynes remain to be developed. We herein report a transition metal-free anti-addition of pinacolborane to alkynes, facilitated by the counteranion effect. This work further develops Chan alkyne reduction by utilizing the borane instead of aluminohydride reagents, enabling the facile synthesis of valuable five-membered boracycles that constitute isosteric alternatives to bioactive butenolides and a versatile platform for abundant downstream transformations. The practical method is distinguished by excellent regioselectivity, a broad substrate scope, and high compatibility with a variety of functional groups. The exploration of trans-selective patterns affords not only a stereo-complementary approach to traditional organic synthesis, but also mandates a new perspective on the noncanonical trans-hydroboration mechanism. A combination of control experiments and computational studies at the DFT level of theory reveal the previously unrecognized role of the HMDS counteranion in a stepwise intermolecular hydrogen transfer process. |
| format | Article |
| id | doaj-art-b6923e5f9f0f4243b16f78f4ba5e1aea |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b6923e5f9f0f4243b16f78f4ba5e1aea2025-08-20T03:22:12ZengNature PortfolioNature Communications2041-17232025-05-0116111210.1038/s41467-025-60052-5Expedient access to bora-butenolide bioisosteres by counteranion-mediated trans-hydroboration of alkynesYuan-Wen Liu0Yu Liu1Yanting Zheng2Mengfan Zhang3Meng-En Ren4Peiyu Hua5Jie Han6Alois Fürstner7Hongming Jin8Jiangsu Key Laboratory of Drug Target Research and Drug Discovery of Neurodegenerative Disease, School of Pharmacy, Nanjing University of Chinese MedicineState Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing UniversityJiangsu Key Laboratory of Drug Target Research and Drug Discovery of Neurodegenerative Disease, School of Pharmacy, Nanjing University of Chinese MedicineJiangsu Key Laboratory of Drug Target Research and Drug Discovery of Neurodegenerative Disease, School of Pharmacy, Nanjing University of Chinese MedicineJiangsu Key Laboratory of Drug Target Research and Drug Discovery of Neurodegenerative Disease, School of Pharmacy, Nanjing University of Chinese MedicineJiangsu Key Laboratory of Drug Target Research and Drug Discovery of Neurodegenerative Disease, School of Pharmacy, Nanjing University of Chinese MedicineState Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing UniversityMax-Planck-Institut für KohlenforschungJiangsu Key Laboratory of Drug Target Research and Drug Discovery of Neurodegenerative Disease, School of Pharmacy, Nanjing University of Chinese MedicineAbstract The hydroboration of alkynes is a textbook example of a syn-selective concerted addition reaction, while trans-selective additions of borane to alkynes remain to be developed. We herein report a transition metal-free anti-addition of pinacolborane to alkynes, facilitated by the counteranion effect. This work further develops Chan alkyne reduction by utilizing the borane instead of aluminohydride reagents, enabling the facile synthesis of valuable five-membered boracycles that constitute isosteric alternatives to bioactive butenolides and a versatile platform for abundant downstream transformations. The practical method is distinguished by excellent regioselectivity, a broad substrate scope, and high compatibility with a variety of functional groups. The exploration of trans-selective patterns affords not only a stereo-complementary approach to traditional organic synthesis, but also mandates a new perspective on the noncanonical trans-hydroboration mechanism. A combination of control experiments and computational studies at the DFT level of theory reveal the previously unrecognized role of the HMDS counteranion in a stepwise intermolecular hydrogen transfer process.https://doi.org/10.1038/s41467-025-60052-5 |
| spellingShingle | Yuan-Wen Liu Yu Liu Yanting Zheng Mengfan Zhang Meng-En Ren Peiyu Hua Jie Han Alois Fürstner Hongming Jin Expedient access to bora-butenolide bioisosteres by counteranion-mediated trans-hydroboration of alkynes Nature Communications |
| title | Expedient access to bora-butenolide bioisosteres by counteranion-mediated trans-hydroboration of alkynes |
| title_full | Expedient access to bora-butenolide bioisosteres by counteranion-mediated trans-hydroboration of alkynes |
| title_fullStr | Expedient access to bora-butenolide bioisosteres by counteranion-mediated trans-hydroboration of alkynes |
| title_full_unstemmed | Expedient access to bora-butenolide bioisosteres by counteranion-mediated trans-hydroboration of alkynes |
| title_short | Expedient access to bora-butenolide bioisosteres by counteranion-mediated trans-hydroboration of alkynes |
| title_sort | expedient access to bora butenolide bioisosteres by counteranion mediated trans hydroboration of alkynes |
| url | https://doi.org/10.1038/s41467-025-60052-5 |
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