Diamine-Tethered Bis(thiourea) Organocatalyst for Asymmetric Henry Reaction

We have developed a novel multifunctional C2-symmetric biphenyl-based diamine-tethered bis­(thiourea) organocatalyst, which was tested in the asymmetric Henry reaction. Under thoroughly optimized conditions, the catalyst provided exceptionally high yields and excellent enantioselectivities especially for electron-deficient aromatic and heterocyclic substrates. Due to a high affinity of the catalyst to silica gel, a simple chromatography-free nitroaldol isolation procedure was feasible. Preliminary kinetic and spectroscopic experiments were performed in order to complete the mechanistic picture of the organocatalyzed nitroaldolization process. Finally, the developed synthetic strategy was successfully applied to the catalytic enantioselective syntheses of enantiopure (S)-econazole and (R)-mirabegron a late-stage intermediate.我们开发了一种新型多功能C₂对称联苯基二胺桥连双(硫脲)有机催化剂，并将其用于不对称亨利反应的催化性能评价。在经充分优化的反应条件下，该催化剂展现出极高的反应收率与优异的对映选择性，尤其针对缺电子芳香族及杂环底物表现突出。得益于该催化剂与硅胶间的高亲和性，可采用无需柱层析的简便硝基羟醛分离流程。为完整阐明该有机催化硝基羟醛化反应的机理，我们开展了初步的动力学与光谱学表征实验。最后，所开发的合成策略成功应用于对映纯(S)-益康唑与(R)-米拉贝隆后期中间体的催化对映选择性合成。