C(sp3)-H键不对称官能化及应用是不对称合成领域公认的挑战性难题之一，其核心是如何调控底物导向基团、手性配体与中心金属的配位强度。已报道的大多数催化体系存在催化活性不高、立体选择性偏低、底物适用范围较窄等不足。本项目采用“边臂效应”策略，拟以二茂铁为骨架，先引入吡唑或咪唑等杂环，再在杂环上引入具有边臂效应的基团，制得一类新型手性二茂铁N ,N配体。边臂基团可调控配体的立体位阻和电子效应，增强配体与中心金属的配位能力，从而提高催化反应的活性和立体选择性。以丁酰胺的C(sp3)-H键不对称官能化反应为模板反应，考察各种手性配体与金属钯形成的催化剂的性能，将较优催化剂应用于手性原料药及中间体的合成中。借助核磁共振谱、DFT计算探究其催化机理，获得边臂基团、配体类型、环状过渡态等因素与催化活性的关联图，揭示其构效关系的一般规律，为C(sp3)-H键不对称官能化反应及应用奠定理论基础。

Asymmetric functionalization and application of C(sp3)-H bonds is one of the most challenging problems in asymmetric synthesis. The key is how to control the coordination strength of substrates, chiral ligands and central metals. Most of the reported catalytic systems have some shortcomings, such as low stereoselectivity, relatively limited substrates and single catalytic mode. Based on the "side arm effect" strategy, a new chiral ferrocenyl-N, N ligands will be designed and prepared by introducing pyrazole or imidazole heterocycles, and then introducing side arm effect groups on these heterocycles. Side arm groups can regulate the stereo resistance and electronic effect of ligands, enhance the coordination ability between ligands and central metals, and thus improve the activity and stereoselectivity of catalytic reactions. The asymmetric functionalization of C(sp3)-H bond of n-butylamide will be used as a model reaction to investigate the catalytic preformance of the complexes formed by various chiral ligands and metal palladium, and the better catalysts will be applied to the synthesis of pharmaceutical intermediates. The catalytic mechanism will be studied by means of NMR and DFT computation. The correlations of among side arm groups, the types of N,N ligands, cyclic transition state with the catalytic activity will be obtained. The general rules of the structure-activity relationship will be revealed, which can give a theoretical support for the application of asymmetric functionalization of C(sp3)-H bonds.