Li Zhenxing, Chen Pengfei, Ni Zhigang, Gao Liuzhou, Zhao Yue, Wang Ranran, Zhu Congqing, Wang Guoqiang, Li Shuhua
State Key Laboratory of Coordination Chemistry, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
Nat Commun. 2025 Jan 16;16(1):735. doi: 10.1038/s41467-025-56000-y.
Chiral binaphthols (BINOL)-metal combinations serve as powerful catalysts in asymmetric synthesis. Their chiral induction mode, however, typically relies on multifarious non-covalent interactions between the substrate and the BINOL ligand. In this work, we demonstrate that the chiral-at-metal stereoinduction mode could serve as an alternative mechanism for BINOL-metal catalysis, based on mechanistic studies of BINOL-aluminum-catalyzed asymmetric hydroboration of heteroaryl ketones. Theoretical calculations reveal that an octahedral stereogenic-at-metal aluminum alkoxide species is the most stable species within the reaction system, and also is the catalytic relevant intermediate, promoting the stereo-determining hydroboration reaction through a ligand-assisted hydride transfer mechanism rather than the conventional hydroalumination mechanism. These computations reproduce the experimental selectivities and also rationalize the stereoinduction mechanism, which arises from the aluminum-centered chirality induced by chiral BINOL ligands during diastereoselective assembly. The reliability of the proposed mechanism could be verified by the single-crystal X-ray diffraction characterization of the octahedral aluminum alkoxide complex. Additional NMR and Electronic Circular Dichroism (ECD) experiments elucidated the behavior of the hexacoordinated aluminum alkoxide in the solution phase. We anticipate that these findings will extend the applicability of BINOL-metal catalysis to a broader range of reactions.
手性联萘酚（BINOL）-金属组合在不对称合成中是强大的催化剂。然而，它们的手性诱导模式通常依赖于底物与BINOL配体之间多种非共价相互作用。在这项工作中，基于对BINOL-铝催化的杂芳基酮不对称硼氢化反应的机理研究，我们证明了金属中心手性立体诱导模式可作为BINOL-金属催化的一种替代机制。理论计算表明，八面体金属中心手性的烷氧基铝物种是反应体系中最稳定的物种，也是催化相关中间体，通过配体辅助的氢化物转移机制而非传统的氢化铝化机制促进立体决定性硼氢化反应。这些计算重现了实验选择性，并合理化了立体诱导机制，该机制源于在非对映选择性组装过程中手性BINOL配体诱导的以铝为中心的手性。所提出机制的可靠性可通过八面体烷氧基铝配合物的单晶X射线衍射表征来验证。额外的核磁共振和电子圆二色性（ECD）实验阐明了六配位烷氧基铝在溶液相中的行为。我们预计这些发现将把BINOL-金属催化的适用性扩展到更广泛的反应范围。
