基于脯氨酸骨架的新型手性季鏻盐催化剂的设计合成及其在不对称合成中的应用

In recent years, chiral quarternary phosphonium salt catalysts become a new direction of phase transfer catalysis, and they can also be organocatalysts applied in asymmetric reactions, more and more attention has been paid by chemists. However, the development of this area is relatively slow due to some natural disadvantages of its own, because only limited examples have been reported, and the application area of these catalysts still needs to be expanded.This project aims to developing several kinds of novel quarternary phosphonium salt catalysts and applying these new catalysts in more asymmetric reactions. Proline skeleton as an excellent and famous chiral induction resource has been widely used in asymmetric catalysis, especially in organocatalysis. We plan to introduce the proline skeleton into the design and synthesis of novel chiral quarternary phosphonium salt catalysts, to prepare several kinds of new catalysts based on prolinol and proline derived chiral diamines. After which, they will first be applied in some model reactions to investigate the catalytic activity of these catalysts. We will further sum up the gerneral laws of the catalytic asymmetric process by the further mechanism study. From the chiral induction aspects, we will look insight into the reaction, consider the complexity of the multi-factor control during the asymmetric catalytic process, make use of the scientific laws summarized into other new asymmetric reactions, especially the reactions which have never been reported yet. This will make the chiral quarternary phosphonium salt catalysts more meaningful in organic synthesis.

近年来手性季鏻盐催化剂成为相转移催化剂发展的一个新方向，同时它们也能用作小分子催化剂应用于不对称合成中而广受关注。但由于自身的一些缺点，导致其发展相对缓慢，同时催化剂种类还比较少，应用范围也有待拓展。本项目将致力于发展几类新型的手性季鏻盐催化剂并将其应用于更多类型的不对称反应当中。脯氨酸骨架是一种广泛用于手性催化，尤其是有机小分子催化中的优秀手性诱导源。本项目计划将其引入到新型手性季鏻盐的设计合成中，拟合成出基于脯氨醇和脯氨酸衍生的二胺的几类新型季鏻盐催化剂。我们首先会将所得催化剂应用于所选定模板反应中，并对其催化性能进行考察，研究其催化机理并总结出相关规律。并进一步从此类催化剂手性控制机理方面入手，综合考虑催化过程中手性诱导过程多因素控制的复杂性，并综合运用所发现和总结的科学规律，将其扩展应用于更多新的不对称催化反应中，尤其是此前尚未有报道的新反应中，使季鏻盐催化剂在有机合成中更具意义。

以脯氨酸手性骨架衍生的手性季膦盐类催化剂为目标化合物，实现了其中一类化合物的合成，并应用于催化不对称反应当中。但脯氨酸二胺季膦盐催化剂在经过多种尝试后仍未成功；鉴于此，我们利用酒石酸、脯氨酸手性骨架进行了一些其他催化剂的设计合成及应用的研究工作。成功设计合成了几种催化剂以及应用在不对称反应当中，实现了几种不对称反应的高效转化，得到了很好的立体选择性。除了计划书中的内容外，我们还对有机小分子催化的不对称合成方面做了一系列的研究工作，采用手性二级胺、卡宾、磷酸等催化剂利用烯胺活化、协同催化等合成策略高选择性地实现了若干新型不对称反应。.过去三年中，发表包括Angew. Chem. Int. Ed., Org. Lett.和J. Org. Chem.等杂志在内的SCI论文8篇。培养硕士研究生8名，其中毕业5名。