基于手性肼骨架的手性配体设计、合成及应用研究

Design and synthesis of novel chiral ligands is an eternal theme in asymmetric metal catalysis. The introduction of hydrazine backbone, which is widely used as chiral auxiliary group, to chiral ligands exhibits various advantages, such as easily tunable structure and versatile coordination modes with transition-metals. However, the research about development of chiral hydrazine ligands and their application in asymmetric catalytic reactions is still a challenging task. It’s long been plagued with several problems including the unstablility of N-N bond leading to low catalytic activity and the rotatation of N-N bond leading to poor chiral induction. In order to address the former challenging issue, we propose the combination of chiral hydrazine backbones with the strong coordinative motifs such as nitrogen or phosphorus skeletons. Furthermore, strategies about introduction of C2-symmetry hydrazines and introduction of hydrazines with coordinative functional groups to the ligands are proposed to overcome the stereoselectivity problem. The catalytic performance of their metal complexes on catalytic asymmetric Heck reactions, asymmetric hydrogenation or hydrosilylation reactions will be explored. The investigation of relationship between the structure of these hydrazine ligands and catalysis activity or selectivity would further provide useful information for the development of more effective ligands.

设计合成结构新颖的手性配体一直是不对称催化研究中的永恒主题。将作为手性辅基而广泛应用的肼骨架引入到手性配体中具有诸多优势，如结构可调性好，与金属作用模式多样等。然而手性肼配体的设计合成及在不对称催化反应中的应用研究仍然是一个具有挑战性的课题。其中的难点有：1）在过渡金属作用下肼骨架中N-N单键不稳定导致作为配体时催化活性较差；2）N-N单键可以发生旋转导致手性诱导能力差。本项目基于“优势骨架合理组合”的配体设计思想，拟通过将手性肼骨架和配位能力强的氮或膦骨架结合起来，以克服肼作为配体时稳定性差的问题；再结合引入具有C2对称性的肼结构和引入具有配位能力官能团的肼结构两种策略，以克服肼作为配体时手性诱导能力差的问题。并探究该类配体的金属络合物在不对称Heck反应、不对称氢化或硅氢化反应中的应用。通过研究手性肼配体的结构和催化活性、反应选择性的构效关系，为进一步设计更为有效的配体提供依据。

催化合成是现代有机合成的核心研究领域，是合成结构多样的有机化合物最直接有效的方法之一。本项目旨在探究一些优势配体骨架的合成工作并将它们应用于新型的催化有机反应中。项目中顺利合成了一系列含磷骨架和含酰基肼骨架的配体，并成功将它们运用于金属铜催化的Ullmann型偶联反应、Chan-Lam反应、含芳基碘基团胺类化合物的去对称化等反应中。同时，还实现了过渡金属铑和钌催化的一系列新型有机反应，如醋酸乙烯酯的乙烯基转移反应和惰性键参与的环化反应等。并且探究了催化剂与反应物之间的作用模式，这些结果为后续进一步揭示金属催化反应的机理奠定了基础。