基于非共价键次级作用协同活化策略发展新型手性双膦配体及其应用研究

手性配体在过渡金属催化的不对称反应中起着重要的作用，在手性配体中引入额外的次级基团能够通过配体与底物之间形成的次级相互作用来提高催化剂的手性控制能力和反应的活性。本项目基于非共价键次级作用协同活化策略，开发一系列结构新颖、拥有自主知识产权的含次级基团氨基、天然氨基酸、手性氨基醇、（硫）脲和手性磷酰胺骨架的新型手性二茂铁双膦配体和手性SPO型二茂铁双膦配体，将其过渡金属催化体系应用于催化不对称[1, n]-负氢迁移/环化反应、分子内去对称化/炔烃异构环化反应、加成/环化反应，期望配体与底物间形成非共价键氢键、离子对相互作用来活化底物，为复杂手性环状分子提供高效的合成方法，针对性地解决反应中的难点问题，获得优异的反应活性和立体选择性，探索催化剂与底物间的相互作用机制。同时运用我们发展的合成方法学为一些重要的手性药物、天然产物和生物活性分子提供新的合成策略。

Chiral ligands played an important role in transition metal-catalyzed asymmetric reactions. The interactions between the ligands and substrates can be enhanced by introducing an additional secondary group into the ligands, which can improve the control ability of chirality and reactivity. On the basis of noncovalent secondary interaction activation strategy, this project will propose to design and synthesize a series of new chiral bisphosphine ligands bearing secondary groups, such as amine, natural amino acid, chiral amino alcohol and phosphoramide groups. And we will apply these new ligands into a series of transition metal-catalyzed asymmetric reactions, such as asymmetric [1, n]-hydride transfer/cyclization, intramolecular desmmetry/alkynl cycloisomerization and addition reaction/cyclization. The noncovalent secondary interactions of hydrogen bonding interaction and ion pair interaction could activate substrates. We will provide efficient synthetic methods for the construction of complex chiral cyclic compounds. We hope we can resolve some difficult problems and afford excellent reactivity and stereoselectivity. We will explore the interaction mechanism between catalysts and substrates. In addition, we will apply these asymmetric catalytic methodologies to prepare some important chiral pharmaceuticals, natural products and biologically active molecules.