新型双功能有机催化剂设计及其催化三氯硅烷不对称还原反应研究

Great progresses have been made in asymmetric organocatalytc reduction by trichlorosilane in the past decade, particularly for the reduction of ketimines and enamines. However, severe limitations still remain with this catalytic reaction system. The substrates are limited to ketimines and enamines bearing a few types of N-aryl and N-alkyl substituents, of which the reduction efficiencies also tend to be less than premium. Meanwhile, the capability of this catalytic reaction system has not been made full use of, which so far is mostly only used for a single step reduction. Moreover, the reaction mechanism remains unclear, and none of the mechanism models proposed in the literature could explain all the experimental observations. On the basis of our significant previous achievements, this proposal aims at developing highly efficient and enantioselective bifunctional new organocatlysts for the asymmetric reduction by trichlorosilane, which could allow for highly effective reductions of the most challenging N-unprotected ketimines and enamines and other new types of substrates, and allow for the development of new casade transformations. Reaction mechanisms will also be one of the most importan focuses in this proposal. Hopefully, a most rational mechanism model could be put forward based on the experimental data, including deuterium labeling results, analytic spectra data of the active species,and data from kinetic studies as well.

手性有机小分子催化三氯硅烷不对称还原经过近十余年来的发展，已经取得了长足的进展，尤其是针对亚胺和烯胺的还原，但该催化反应体系还存在明显的局限性和不足，只能对N原子上带有少数几种芳基或烷基的底物获得好的结果，而且催化效率偏低；同时，反应类型也基本上局限于单步还原反应，缺乏创新的底物和反应类型；另外，反应机理也不清楚，一些实验现象也无法用现有的机理模型进行解释。本研究拟在扎实的前期工作基础上，针对三氯硅烷不对称还原，发展高性能的新型手性双功能有机催化剂，实现对N原子不带取代基的亚胺和烯胺的高效高对映选择性还原，同时，发展出新的底物和串联反应类型，并结合标记实验、波谱学和反应动力学等手段，揭示反应机理信息，并最终提出最合理的反应机理模型。

手性有机小分子催化三氯硅烷不对称还原已经取得了长足的进展，尤其是针对亚胺和烯胺的还原，但该催化反应体系还存在明显的局限性和不足，只能对N原子上带有少数几种芳基或烷基的底物获得好的结果，而且催化效率偏低；同时，反应类型也基本上局限于单步还原反应，缺乏创新的底物和反应类型；另外，反应机理也不清楚，一些实验现象也无法用现有的机理模型进行解释。本研究在扎实的前期工作基础上，针对三氯硅烷不对称还原，发展了高性能的新型手性双功能有机催化剂，实现对N原子不带取代基的亚胺和烯胺的高效高对映选择性还原，同时，发展出了新的底物和串联反应，还原胺化等新反应。并结合标记实验、波谱学和反应动力学等手段，揭示反应机理信息。