Liu Yuan-Wen, Liu Yu, Zheng Yanting, Zhang Mengfan, Ren Meng-En, Hua Peiyu, Han Jie, Fürstner Alois, Jin Hongming
Jiangsu Key Laboratory of Drug Target Research and Drug Discovery of Neurodegenerative Disease, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
State 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 University, Nanjing, China.
Nat Commun. 2025 May 27;16(1):4897. doi: 10.1038/s41467-025-60052-5.
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.
炔烃的硼氢化反应是顺式选择性协同加成反应的典型教科书示例,而硼烷对炔烃的反式选择性加成反应仍有待开发。我们在此报告了一种无过渡金属的频哪醇硼烷对炔烃的反式加成反应,该反应受抗衡阴离子效应的促进。这项工作通过使用硼烷而非氢化铝试剂进一步拓展了Chan炔烃还原反应,能够简便地合成有价值的五元硼杂环,这些硼杂环构成了生物活性丁烯内酯的等排体替代物以及丰富的下游转化反应的通用平台。该实用方法具有出色的区域选择性、广泛的底物范围以及与多种官能团的高兼容性。对反式选择性模式的探索不仅为传统有机合成提供了一种立体互补方法,还促使人们对非经典反式硼氢化反应机理有了新的认识。一系列对照实验和密度泛函理论(DFT)水平的计算研究揭示了六甲基二硅氮烷(HMDS)抗衡阴离子在逐步分子间氢转移过程中此前未被认识到的作用。