金鸡纳生物碱衍生的多官能手性膦氮配体和金属协同催化不对称反应的研究

The design and synthesis of stable, low cost and highly efficient chiral ligands and catalysts remain to be one of the core of the tasks in the field of asymmetric catalysis. It is of great significance to develop a new catalytic system and explore the relationship between the ligand structure and its catalytic ability. In this project, a series of cinchona-derived novel multifunctional P,N-ligands will be developed and synthesized, leading to a new catalytic system via the appropriate combination of designed chiral P,N-ligands and metal reagents. Through controlling the reaciton transition state by the way of dual activation, the coresponding effective chiral environment will be produced. This catalytic system will be used to study various asymmetric reactions, such as allylic alkylation reaction、[2+2] cycloaddition reaction of imine and aldehyde and Conia-.Ene reaction of terminal alkyne and allene. Using the tunable characteristics between P,N-ligands and metal reagents is to modify the catalyst system, optimize the reaction conditions, explore them to catalyze the various types of reaction with high selectivities and study the initial mechanism of the catalysts in the reaction, including the law and intinsic relation of multiple interactions between the catalysts、 catalysts and substrates and the catalytic active species and media.

合成稳定、低成本和高效率的手性配体及催化剂的设计一直是不对称催化领域的核心任务之一，而发展新的催化体系，研究配体结构与催化性能之间的关系更具有重要的意义。本项目将设计和合成一类基于金鸡纳生物碱骨架的新型多官能手性膦氮配体，通过将不同结构的手性膦氮配体与金属结合形成新的催化体系，通过双活化策略共同控制反应中间的过渡态，产生有效的相应手性环境。这类催化体系被用来研究相关的不对称反应，例如烯丙基烷基化反应、亚胺及醛的[2+2]环加成反应、末端炔及联烯的Conia-Ene反应等。利用手性膦氮配体和金属可调控的特点修饰催化体系，优化反应条件，探索出能对各类反应取得高选择性的相关催化体系和反应条件，并研究催化剂在反应中的初步机理，包括催化剂之间、催化剂与底物以及催化活性物种与介质之间的多重相互作用的规律和内在联系。

膦氮原子与金属配位具有独特的优势，历年来，围绕配体骨架结构设计了很多的手性膦氮配体，而多官能手性膦氮配体却鲜有报道。本项目设计和合成了生物碱、1,2-环己二胺，1，2-二苯基乙二胺和alpha-氨基酸等骨架的新型多官能手性膦氮配体，通过将不同骨架的手性膦氮配体与金属结合形成新的多功能催化体系，协同催化不对称反应，例如烯丙基化反应、亚胺的[2+2]环加成反应、偶氮甲碱叶立德的[3+2]环加成反应、异氰酸酯与醛的aldol反应、Mannich-炔氢氨化串联反应、末端炔的Conia-Ene反应等。而且，进一步探索了对各类反应取得高选择性的催化体系和反应条件，并研究催化剂在反应中的初步机理，包括催化剂之间、催化剂与底物以及催化活性物种与介质之间的多重相互作用的规律和内在联系。研究结果表明：手性膦氮配体与金属协同催化偶氮甲碱叶立德的[3+2]环加成反应和异氰酸酯与醛的aldol反应中表现出较好的催化活性和立体选择性。