配位功能化手性膦配体的合成和应用

Chiral phosphines play a vital role in ligand-controlled asymmetric catalysis. Typical modifications of chiral phosphine mainly rely on the selection of ligand backbone and the electronic property of coordinating atom. However, after years of development, these modifications have to face some limitations, especially in some challenging reactions. Chiral phosphine with coordinating function is a totally different type of modification that is inspired by the synergistic catalysis of enzyme. An additional interaction between the ligand and the substrate is introduced to increase the reactivity and selectivity of the reaction. However, the development of this is very limited up to date, including not only types of ligands but also types of substrates and reactions. This application will try to develop a series of new chiral phosphines with coordinating functions. Then investigations of their applications in various reactions and asymmetric syntheses of bioactive molecules will be carried out.

手性膦配体在配体控制的不对称催化中占据着极为重要的地位。手性膦配体的传统修饰方式主要局限于配体骨架的改变和配位原子电性的调整。经过多年的发展，这类方式已经面临一定的瓶颈，难以满足日益增加的新的需求。手性膦配体的功能化是基于酶协同催化的理念，在配体上增加额外的和底物的相互作用来提高反应的活性和选择性。作为一种完全不同于传统的修饰方式，目前这方面的研究还非常少。不仅配体的种类局限，而且可以适用的底物和反应类型更是面临较多的挑战。本项目拟在前期发现的基础上，发展一系列新型骨架的配位功能化手性膦配体，来尝试解决不对称催化反应中存在的一些难题，并利用新方法进行生物活性分子的合成和活性测试。

我们围绕配位功能化手性膦配体的合成和应用这一目标进行了膦配体的精心设计和广泛尝试。第一，设计了双官能化的膦氧配体，构建了双金属催化剂，实现了各类C-H键活化反应，并获得了高的反应收率和立体选择性。第二，利用弱相互作用，发展了现场组装的配位功能膦配体，实现了C-C键活化反应和烯醛偶联反应，展示了该体系独特的反应性。第三，研究了类膦配体——N-杂环卡宾配体的功能化，发展了双功能化的卡宾配体，解决了吡啶C3-烯基化反应这一长期的挑战。共发表了SCI论文28篇，包括影响因子大于10的论文15篇，包括Nat Chem 1 篇，Nat Commun 4篇，J. Am. Chem. Soc 2篇，Angew. Chem. Int. Ed 4篇。