基于手性Lewis碱的新“受阻Lewis酸碱对”催化体系研究

Frustrated Lewis pairs (FLPs) chemistry is a powerful solution for the non-metal catalyzed stereoselective hydrogenations and hydrosilylations. Up to date, the development of chiral FLP catalysts mainly focused on the exploration of chiral Lewis acidic components and some breakthroughs have been made. Dilemmas, such as possessing a long, exhausting and difficult synthetic route, fewer variety and moisture-sensitive, et. al., tax greatly. Otherwise, it remains inact for the non-metal catalyzed hydrogenations and hydrosilylations of the electron-deficient substrates. On the contrary, chiral Lewis basic materials are abundant in nature and stable, which gives a big application potential in the FLP chemistry. Herein, we are willing to introduce chiral Lewis bases into FLP chemistry further. Chiral Lewis bases such as thiourea and cinchona alkaloids will be employed, then matching with different Lewis acidic components to develop new FLP systems with Lewis bases as chirality origin. This novel FLP system would be studied and applied in the non-metal catalyzed hydrogenations and hydrosilylations of unsaturated substrates including some challenging electron-deficient ones. Combination of theoretical calculation and experimental studies will be conducted to investigate the impact of substitutents and steric effects on reaction activities and stereoselectivity. Later, modification of the catalysts will be conducted based on the mechanism information to develop some highly efficient novel chiral FLP catalysts.

“受阻Lewis酸碱对”（FLPs）化学是解决非金属催化不对称氢化、硅氢化反应的一种有效途径。迄今为止，手性FLP催化剂的发展集中于对手性Lewis酸的探索上，取得了很多成果但也存在如合成路线长、难度大，催化剂种类少，对水、氧较为敏感等不足，此外针对挑战性缺电子不饱和底物的催化氢化、硅氢化反应还尚未解决。相比之下，手性Lewis碱资源丰富、性质稳定，具有较强的应用潜力。在本项目中，申请人拟将多种手性Lewis碱引入FLP化学，与不同酸性的Lewis酸进行匹配，设计、发展以Lewis碱作为手性来源的新型手性FLP催化剂，研究其在立体选择性非金属催化氢化、硅氢化反应中的应用，并挑战缺电子不饱和底物。再结合理论计算与实验研究手段，研究取代基效应、位阻作用等对反应活性和立体选择性的影响，并基于机理信息对催化剂结构进行优化，从而发展一类具有新催化模式的高效手性FLP催化体系。

手性Lewis碱在自然界中资源丰富、性质稳定，也可以通过简单的化学转化来快速构建得到。我们将手性噁唑啉等引入FLPs化学，发展了一类以Lewis碱作为手性来源的新型FLPs催化体系，并利用该型催化剂完成了对多种不饱和底物（特别是挑战性缺电子型底物）的高立体选择性催化氢化（硅氢化）反应；发展了由“非手性FLPs催化剂启动，手性质子梭构建手性中心”的“接力式”混合催化模式，拓宽了底物适用范围，实现了这一研究领域的重要突破。发表项目相关研究论文7篇，综述1篇，含Angew. Chem., Int. Ed. 1篇，Org. Lett. 2篇，J. Org. Chem. 1篇，Chem. Comm. 1篇，Tetrahedron Lett. 1篇，Chinese J. Chem. 2篇。