Liu Wenjun, Ren Caiyi, Zhou Liyuan, Luo Haotian, Meng Xiangjian, Luo Peng, Luo Yingkun, Dong Wennan, Lan Shouang, Liu Jinggong, Yang Shuang, 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, Fujian College, University of Chinese Academy of Sciences, Fuzhou 350100, China.
Fujian Normal University, Fuzhou 350108, China.
J Am Chem Soc. 2024 Jul 24;146(29):20092-20106. doi: 10.1021/jacs.4c04171. Epub 2024 Jul 15.
Developing a general method that leads to the formation of different classes of chiral bioactive compounds and their stereoisomers is an attractive but challenging research topic in organic synthesis. Furthermore, despite the great value of asymmetric transfer hydrogenation (ATH) in both organic synthesis and the pharmaceutical industry, the monohydrogenation of unsymmetrical 1,2-diketones remains underdeveloped. Here, we report the aryloxy group-assisted highly regio-, diastereo-, and enantioselective ATH of racemic 1,2-diketones. The work produces a myriad of enantioenriched dihydroxy ketones, and further transformations furnish all eight stereoisomers of diaryl triols, polyphenol, emblirol, and glycerol-type natural products. Mechanistic studies and calculations reveal two working modes of the aryloxy group in switching the regioselectivity from a more reactive carbonyl to a less reactive one, and the potential of ATH on 1,2-diketones in solving challenging synthetic issues has been clearly demonstrated.
开发一种能生成不同类别手性生物活性化合物及其立体异构体的通用方法，是有机合成中一个引人关注但具有挑战性的研究课题。此外，尽管不对称转移氢化（ATH）在有机合成和制药行业都具有巨大价值，但不对称1,2 - 二酮的单氢化反应仍未得到充分发展。在此，我们报道了芳氧基辅助的外消旋1,2 - 二酮的高度区域、非对映和对映选择性ATH反应。该工作产生了大量对映体富集的二羟基酮，进一步的转化提供了二芳基三醇、多酚、恩布利醇和甘油型天然产物的所有八种立体异构体。机理研究和计算揭示了芳氧基在将区域选择性从反应性较高的羰基切换到反应性较低的羰基方面的两种工作模式，并且清楚地证明了1,2 - 二酮的ATH在解决具有挑战性的合成问题方面的潜力。
