自组装有机手性超分子催化剂的构建及其性能研究

The polymeric diol compounds with chain and conformationally flexible structure have been attracting increasing interest in recent years. In organocatalysis，such compounds were widely used as a kind of soluble polymeric support for the organocatalysts. But the possibility that the polymer scaffold may display unique stereodiscrimination processes around the organocatalysts has been almost ignored. Furthermore, recent findings from the proposer have shown that a new kind of chiral supramolecular organocatalyst,self-assembed from the protonated chiral amines and achiral polymeric diol compounds, was disclosed.The resulting self-assemblies were found to be excellent catalytic performance and prospect in the asymmetric catalysis.Under this concept,this project will work on the following four main aspects: (a) Three kinds of chiral supramolecular catalyst will be designed and prepared by simply self-assembling of chiral polymeric diol compounds with chiral or achiral amines and achiral polymeric diol compounds with chiral amines.(b) The formation mechanism and steric interactions between the amines and the polymeric diol compounds of the supramolecular chiral catalyst will be clarifid in detail.(c) The properties and activation mechanism of the supramolecular chiral catalysts will be discovered.(d) Further applications of the supramolecular chiral catalysts in the asymmetric reactions and asymmetric total synthesis of target natural products or known compounds of biological and pharmaceutical relevance will be explored.The successful development of the proposed methodologies will have some positive impact on the preparation of chiral supramolecular compounds and the development of supramolecular chemistry and organocatalysis.

具有链状弱刚性结构的聚二醇化合物近年来引起科学家的广泛关注。在有机催化中，研究者的注意力大多集中在其可作为一类可溶性聚合物载体，而很少意识到其可能是影响催化剂催化性能的一个重要结构因素。申请人在前期研究中证明了非手性聚二醇可与质子化手性胺形成手性超分子催化剂并展示了其优异的催化性能和应用前景。本项目拟利用这一特性，采用手性聚二醇与手性或非手性胺以及非手性聚二醇与手性胺自组装的方法，制备三类手性超分子催化剂；阐明手性超分子催化剂的形成原理以及在空间上的作用机理；探索手性超分子催化剂在不对称反应中的催化性能、作用原理以及应用；实现催化一些较难的不对称反应并合成相关天然化合物及其基础骨架。本课题在制备结构可控的手性超分子化合物、发展超分子化学和丰富有机催化等方面都有一定意义。

具有链状弱刚性结构的聚二醇化合物近年来引起科学家的广泛关注。在有机催化中，研究者的注意力大多集中在其可作为一类可溶性聚合物载体，而很少意识到其可能是影响催化剂催化性能的一个重要结构因素。申请人在前期研究中证明了非手性聚二醇可与质子化手性胺形成手性超分子催化剂并展示了其优异的催化性能和应用前景。本项目获得国家自然科学基金青年基金（No. 21202149）资助后，申请人利用这一特性，采用手性聚二醇与手性胺以及非手性聚二醇与手性胺自组装的方法，制备了二类手性超分子催化剂；通过进一步研究发现该类超分子催化剂可以催化不对称Diels-Alder反应、Michael反应和Mannich反应；同时发展了一些操作简便、反应条件温和、经济、选择性高的不对称新反应的新有机合成方法学，实现催化一些较难的不对称反应并合成了一些药物、天然化合物及其基础骨架（Detrusitol、cycloalkano[b] fused pyrrolidines、Dapoxetine、3,4-disubstituted dihydro-2(1H)-quinolinones、tetrahydroxanthenones、chromanes、bicyclic Lactams、oxabicyclo [2.2.2] octanes和 monohaloalkenes）；在Adv. Synth. Catal.等国际期刊发表研究论文5篇；另发表未标注基金号的SCI论文5篇；申请发明专利5项；培养研究生13名。