State Key Laboratory of Synthetic Chemistry, Department of Chemistry, The University of Hong Kong, Hong Kong 00000, China.
J Am Chem Soc. 2022 Apr 20;144(15):6918-6927. doi: 10.1021/jacs.2c01380. Epub 2022 Apr 7.
Desymmetrization of easily available disubstituted malonic esters is a rewarding strategy to access structurally diverse quaternary stereocenters. Particularly, asymmetric reduction of malonic esters would generate a functional group with a lower oxidation state than the remaining ester, thus allowing for more chemoselective derivatization. Here, we report a new set of conditions for the zinc-catalyzed desymmetric hydrosilylation of malonic esters that afford aldehydes as the major product. Compared with alcohol-selective desymmetrization, the partial reduction uses a higher concentration of silanes and new pipecolinol-derived tetradentate ligands, proposedly to switch the pathway of zinc hemiacetal intermediates from elimination to silylation. As a result, high aldehyde-to-alcohol ratios and enantioselectivity of aldehydes are obtained from malonic esters with a large collection of substituents. Together with the abundant reactivity of aldehydes, the partial reduction has enabled an expeditious synthesis of bioactive compounds and natural metabolites containing a quaternary stereocenter.
容易获得的二取代丙二酸酯的去对称化是一种很有价值的策略，可以构建结构多样的季立体中心。特别是丙二酸酯的不对称还原会生成一个比剩余酯基氧化态更低的官能团，从而允许更具化学选择性的衍生化。在此，我们报告了一组新的条件，用于锌催化的丙二酸酯不对称硅氢化反应，得到醛作为主要产物。与醇选择性去对称化相比，部分还原使用了更高浓度的硅烷和新的哌啶醇衍生的四齿配体，据推测这是为了将锌半缩醛中间体的反应途径从消除转变为硅烷化。结果，从具有大量取代基的丙二酸酯中得到了高醛醇比和醛的对映选择性。加上醛的丰富反应性，部分还原已经能够快速合成含有季立体中心的生物活性化合物和天然代谢物。
