Zhao Zhifei, Dong Wennan, Liu Jinggong, Yang Shuang, Cotman Andrej Emanuel, Zhang Qi, Fang Xinqiang
State Key Laboratory of Structural Chemistry, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences, Fuzhou 350100, China.
Orthopedics Department, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, China.
J Am Chem Soc. 2024 Dec 11;146(49):33543-33560. doi: 10.1021/jacs.4c11070. Epub 2024 Nov 27.
Asymmetric transfer hydrogenation (ATH) has been recognized as a highly valuable strategy that allows access to enantioenriched substances and has been widely applied in the industrial production of drug molecules. However, despite the great success in ATH of ketones, highly efficient, regio- and stereoselective ATH on enones remains underdeveloped. Moreover, optically pure acyloins and 1,2-diols are both extremely useful building blocks in organic synthesis, medicinal chemistry, and materials science, but concise asymmetric approaches allowing access to different types of acyloins and 1,2-diols have scarcely been discovered. We report in this paper the first highly efficient ATH of readily accessible β,γ-unsaturated α-diketones. The protocol affords four types of enantioenriched acyloins and four types of optically pure 1,2-diols in highly regio- and stereoselective fashion. The synthetic value of this work has been showcased by the divergent synthesis of four related natural products. Moreover, systematic mechanistic studies and density functional theory (DFT) calculations have illustrated the origin of the reactivity divergence, revealed the different roles of aromatic and aliphatic substituents in the substrates, and provided a range of unique mechanistic rationales that have not been disclosed in ATH-related studies.
不对称转移氢化（ATH）已被公认为是一种极具价值的策略，可用于获得对映体富集的物质，并已广泛应用于药物分子的工业生产中。然而，尽管酮的不对称转移氢化取得了巨大成功，但对于烯酮的高效、区域和立体选择性不对称转移氢化仍未得到充分发展。此外，光学纯的偶姻和1,2 -二醇在有机合成、药物化学和材料科学中都是极为有用的结构单元，但几乎尚未发现能够获得不同类型偶姻和1,2 -二醇的简洁不对称方法。我们在本文中报道了首例易于获得的β,γ -不饱和α -二酮的高效不对称转移氢化反应。该方法以高度区域和立体选择性的方式提供了四种类型的对映体富集偶姻和四种类型的光学纯1,2 -二醇。这项工作的合成价值已通过四种相关天然产物的发散合成得到了展示。此外，系统的机理研究和密度泛函理论（DFT）计算阐明了反应活性差异的起源，揭示了底物中芳香族和脂肪族取代基的不同作用，并提供了一系列在不对称转移氢化相关研究中尚未披露的独特机理依据。
