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.

本研究开发了一种新型多功能C₂对称联苯骨架、经二胺锚定的双(硫脲)有机催化剂，并将其应用于不对称亨利反应的性能测试。在经过全面优化的反应条件下，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。由于该催化剂与硅胶具有较高的亲和性，无需色谱层析即可实现硝基醛醇产物的简便分离。为完整阐明该有机催化硝基醛醇化反应的机理，本研究开展了初步的动力学与光谱学实验。最后，本研究所开发的合成策略已成功应用于光学纯(S)-艾康唑与(R)-米拉贝隆后期中间体的催化对映选择性合成。