廉价金属催化的基于碳氢键活化的不对称串联反应

Transition metal-catalyzed C-H activation reaction has emerged as one of the most important and powerful tool in organic synthesis for the construction of C-C and C-X bonds. Especially, the recent cascade reactions involved C-H bond activation have provided a more effective and diverse synthetic methodology for the synthesis of complex functional organic motifs. However, challenges remain in this field: the use of precious metal catalysts in the reaction is not consistent with the concept of green and economic chemistry; the asymmetric cascade reactions involved C-H bond activation is rare, which makes the application of this strategy limited greatly. In this project, we will investigate the low-cost transition metals, such as Co, Ni, Fe, Cu, and other promising metals, catalyzed asymmetric cascade reactions involved C-H bond activation. We will design and exploit a series of chiral ligands in order to realize the asymmetric cascade reactions with unactivated C-H bonds and polarized unsaturated bonds, thus constructing the important functional molecular scaffolds, such as chiral amino acids and chiral heterocycles, etc., with high efficiency, high selectivity and environment benign. We will test the reactivity and selectivity of the catalytic C-H transformations, and get insight into the reaction mechanisms. We will summarize the reaction characteristics and regularity, by providing more reasonable approaches for the construction of more complex functional chiral molecular and expanding the scope of catalytic C-H bond transformations.

过渡金属催化的碳氢键活化反应作为一类重要的构筑碳碳键和碳杂键的手段，已经发展成为有机合成化学的重要研究领域。特别是近年来发展的基于碳氢活化的串联反应，为复杂功能性有机结构单元的构建提供了更加高效和多元化的合成路线。然而当前该领域的发展仍然面临着挑战：贵金属催化剂的使用使得相应催化体系具有较低的绿色经济性；截止目前，有关碳氢键参与的不对称串联反应鲜有报道，大大限制了该类方法的广泛应用。本项目拟开展廉价金属催化的基于碳氢键活化的不对称串联反应研究，采用不同廉价金属如Co、Ni、Fe、Cu等，利用各种手性配体，实现惰性碳氢键和极性不饱和键参与的不对称串联反应，高效、高选择性、环境友好的构建手性氨基酸和手性杂环等重要功能性分子骨架。探索研究相关催化反应的活性和选择性，深入探究反应机理，总结其反应特点和规律，为更加复杂功能手性分子骨架的构建提供更加合理的合成方法，从而拓展催化碳氢键转化反应的范围。

过渡金属催化碳氢键不对称官能化反应现已发展成为一类重要的手性分子合成工具，本课题旨在结合最新催化合成策略，开发新型催化碳氢键活化体系, 从而高效多样性构建功能分子结构单元。其中主要研究成果有：1）率先发展催化碳氢键不对称转化高效构建氮-碳轴手性策略；2）首次开发钯(II)催化双碳氢键不对称环化多样性构建轴手性分子策略，并实现其催化应用；3）经催化碳氢键选择性官能化反应，实现一系列功能结构单元的高效构建。其中，不对称催化反应的相关应用研究仍在进行中。综上所述，本研究不仅是催化碳氢键不对称转化反应的重要补充，更重要的是为各类功能分子的合成以及不对称催化的可持续发展提供了新路径。项目资助发表SCI论文5篇，待发表论文3篇。培养研究生4名，其中2名已经取得硕士学位，2名在读。项目投入经费24万元，支出17.682516万元，各项支出基本与预算相符。剩余6.317484万元经费将投入本项目的后续研究。