新型手性P/N配体的设计合成及不对称催化性能研究

As a part of our continuous efforts toward the development of new and practical chiral ligands for use in the asymmetric reaction of challenging substrates, the present project will focus on: 1) the design and synthesis of new chiral P/N ligands which contained a oxazoline backbone and their application in the catalytic asymmetric Herry reaction; 2) the investigation of the relationship between the structure of these P/N ligands and their catalytic activities in the Cu-catalyzed asymmetric Herry reaction; 3) extending the application of chiral P/N ligands in asymmetric catalysis.. By comparing the catalytic activities and enantioselectivities of various P/N ligands, the rationale of the relationship between the ligand structure and catalytic efficiency will be summarized and guide the design of new generation of chiral P-ligands.. To further extend the application of chiral P/N ligands in asymmetric reaction, some new or challenging substrates will be synthesized and submitted to the catalytic asymmetric Herry reaction with these P/N ligands. The potential use of these P/N ligands in chemical industry will be evaluated. The application of P/N ligands in other challenging catalytic reaction such as asymmetric 1,3-dipolar cycloaddition reaction and asymmetric propargylic substitution reaction will also be examined, which is expected to give good results.

本项目旨在通过简短的合成步骤，将噁唑啉杂环引入到手性配体的结构中而设计合成一类新型手性P/N配体，通过系统考察磷配位原子上的取代基、配体骨架结构等对不对称催化反应活性和立体选择性的影响，探索该类手性配体的结构与不对称催化反应性能间的关系，总结规律性认识，指导新配体的设计。在新配体的应用研究方面，以烯丙基取代反应为起点，并重点开展这些手性配体在一些具有挑战性的、具有一定难度的不对称催化反应，如高位阻的硝基烷烃与醛（酮）的不对称Herry反应、不对称[3+2]环加成反应以及炔丙醇酯的胺化反应等中的应用，推出具有创新特色的研究成果。

本研究工作包含：(1)用简单的方法合成了14个手性希夫碱N,O-配体，以及用硼氢化钠还原配体L1得到的手性配体L15。将合成的15个手性配体在不对称Herry反应中的应用进行了初步的探索，发现该类手性配体在硝基甲烷对各类醛的不对称Henry反应中表现出了一定的手性诱导能力，最高获得了98%的ee值。(2)对手性膦酸脂的合成研究进行了一定的拓展探索，以不对称氢化的方式对α,β-不饱和磷酸酯进行不对称催化氢化获得手性膦酸脂，最高获得了92%的ee值；对β,γ-不饱和磷酸酯进行不对称催化氢化获得手性膦酸脂，最高获得了87%的ee值。(3)以手性P/N配体及Cu形成的配合物为催化剂，对炔丙醇酯的不对称脱羰基胺化反应进行了探索；同时对烯丙醇的不对称催化氢化进行了探讨。该研究工作的进行，对手性配体的设计及其应用提供了一定的参考价值。