新型P-手性膦配体以及挑战性底物的高效不对称氢化研究

Asymmetric hydrogenation is one of the most challenging and successful reactions in asymmetric catalysis. However, the scope of substrates is still quiet limited for this transformation. Aimed at challenging (difficult) substrates, we have successfully developed few excellent ferrocene-based P-chiral phosphine ligands, such as TriFer, ChenPhos and C1-TriFer. Some of our results have been published on J. Am. Chem. Soc.，Angew. Chem. Int. Ed. and Chem. Commun. or disclosed in the patents. On the basis of our previous research, this project focuses on highly efficient asymmetric hydrogenation of challenging substrates. Wide-bite-angle or trans-chelating ferrocene-based P-chiral ligands, bearing secondary interaction functional groups for secondary interaction with substrates, would be designed and synthesized, and their performance (enantioselectivities and catalytic activities) in asymmetric hydrogenation would be evaluated. It would be systematically investigated for the first time that the influence of the bite angles of a series of wide-bite-angle or trans-chelating P-chiral ligands on enantioselectivities and catalytic activities in asymmetric hydrogenation, the relationship among the novel chiral ligands' structure, enantioselectivities and catalytic activities, and the influence of ligands' scaffold, donor atom, electronic and steric effects, metal and substrates' structure on enantioselectivities and catalytic activities.

不对称催化氢化反应是手性催化研究领域最富有挑战的和突出成果的反应。然而，适应该反应的"容易底物"还有很大局限性。申请者将"挑战性底物"作为主攻方向，已成功发展了以二茂铁为骨架的优秀的手性膦配体TriFer、ChenPhos 和C1-TriFer，部分结果已在J. Am. Chem. Soc.，Angew. Chem. Int. Ed. 等杂志上发表或在专利中公开。在此基础上，本项目以发展挑战性底物的高效不对称氢化为核心目标，设计、合成以二茂铁为骨架结构C2-对称,C1-对称两个系列新型大咬角和反式螯合P-手性膦配体和催化剂，系统地研究催化活性和对映选择性；系统地探索对配体和催化剂的咬角、第二相互作用官能团的类型、与中心金属原子间的距离以及配体骨架、取代基的电子和立体效应、以及底物结构等因素对手性诱导和催化活性的影响规律性，为新一代配体和催化剂的设计提供理性指导。

在这一项目中，我们首先发展了一种二茂铁类膦配体的简便、高度可积木化合成新方法。在此基础上，设计合成了大量二茂铁类手性配体和催化剂。虽然所设计合成的二茂铁类大咬角或反式螯合的P-手性膦配体在Rh-催化的不对称氢化中表现不令人满意，但所发展的许多二茂铁类配体和催化剂在众多催化不对称反应中，如Pd-催化的不对称烯丙基烷基化、双功能膦催化的分子间和分子内MBH反应、硫脲-胺催化的不对称Michael加成等，表现出很好的结果。本项目对二茂铁类催化剂的开发进行了有益的探索，为手性催化剂设计提供更多的结构模式，基本上完成了本项目的研究目标。