手性聚(2-噁唑啉)的可控合成及其不对称有机催化性能

Inspired by nature, the asymmetric organic catalysis using synthetic polypeptides and helical chiral polymers has emerged over the last years as an attractive new approach to asymmetric catalysis, which is mainly owing to the fact that such polymeric scaffolds can provide a chiral microenvironment for a catalyst that is analogous to an enzyme active site. To date, the synthetic chiral polymers have generally not achieved the same level of activity and/or selectivity in catalysis compared with biopolymers. One main reason is that they have less functional diversity and are structurally less well defined resulting from the poor controllability of chemical synthesis. On the other hand, the main-chain chiral poly(2-oxazolines) can be regarded as pseudo- polypeptides and, therefore, it might be anticipated that they could form secondary structures. Furthermore, these polymers can be obtained via a living cationic ring-opening polymerization (CROP) of the corresponding monomers with a substituent on the 4th or 5th position. Apparently, the living polymerization characteristic would facilitate the design and synthesis of the functional polymers with well-defined structure. Taken together, it can be envisioned that main-chain chiral poly(2-oxazolines) are probably a promising and attractive candidate for enantioselective catalysts. In this proposed project we will take advantage of living CROP to synthesize novel chiral poly(2-oxazolines) bearing proline pendants through the bottom-up strategy combining with the azide-alkyne click chemistry. With the aim of realizing the idea, the functional molecules, including prolinamide-substituted 2-oxazolines and alkynyl analogs, azido derivatives of proline, and special initiators have been designed. One crucial issue have to face and should be investigated in the project is the good control of the ring-opening polymerization of these functional 2-oxazolines to obtain the desired polymers with predefined structure and composition. Subsequently, the investigations on the secondary structure, the self-assembly behavior of amphiphilic copolymers, the responsivity to external stimulus such as temperature, pH, and solvents, will be conducted in detail. The direct intermolecular aldol reaction between acetone and 4-nitrobenzaldehyde would be chosen as the benchmark to evaluate the performance of the poly(2-oxazolines)-based catalysts and identify the optimum conditions under catalysis. Another task of the project is to examine the relationship between the main-chain chirality of poly(2-oxazolines) and their catalytic activity as well as selectivity and thus further enable understanding and improving their performance. We hope that this research would provide a new avenue in the development of efficient polymer-based asymmetric catalysts and metal-free organic catalysis.

基于合成聚肽和螺旋手性聚合物的不对称有机催化是当前高分子科学与催化领域交叉的热点研究方向.本项目根据环状亚胺醚衍生物普遍具有活性开环聚合的特性，设计新颖的脯氨酰基取代和炔基取代的2-噁唑啉功能单体，运用自下而上并结合点击化学后功能化策略，合成一系列具有拟聚肽结构的手性聚(2-噁唑啉)衍生物.详细研究聚合反应特征，掌握可控制备方法和结构调控手段；系统考察聚合物的溶解性能、溶液状态下的链构象及可能形成的高层次规整结构、两亲嵌段共聚物的自组装行为及其聚集体对环境刺激的响应性；以分子间直接醇醛缩合反应为对象考察上述手性聚合物的不对称催化性能，探讨聚合物主链/侧链构型、取代基性质对催化位点的立体化学协调作用，揭示聚合物二次结构、拓扑类型、聚集体形态及反应条件对催化活性和对映选择性的影响规律、阐释手性诱导和不对称催化机理，为探索新型手性聚合物基不对称催化剂、建立无金属参与的有机催化方法提供新的途径.

对映选择性有机催化已经成为与过渡金属催化和酶催化具有同等地位的实现不对称合成的重要方法。随着有机催化研究的不断深入，有机小分子催化剂的固定化，特别是以聚合物为载体的负载型有机催化剂的研究吸引了广泛关注。将有机催化基团键接到聚合物骨架上不仅有利于催化剂的回收利用，而且更为重要的是，聚合物基材作为催化体系的有机组成部分会显著影响催化活性和立体选择性。本项目以2-噁唑啉活性/可控开环聚合为设计平台，采用“自下而上”合成策略，制备了结构明确的侧链含有L-脯酰胺/吡咯烷单元的一系列聚（2-噁唑啉）衍生物，详细考察了这些聚合物在Aldol、Michael反应中的不对称催化性能以及构-效关系。主要研究内容和成果如下：1）首次将三氟甲磺酸稀土盐用于引发2-噁唑啉单体开环聚合，在温和的常规加热条件下实现了活性/可控聚合，阐明了引发、增长机理；此类稀土引发剂适用单体范围较宽、聚合速率快，克服了常用引发体系需用微波辅助、不易放大制备规模且引发剂毒性较大等缺点，可望应用于新型聚噁唑啉功能材料的研究领域。2）以环己酮-对硝基苯甲醛Aldol反应为模型，系统考察了不同结构的聚（2-噁唑啉）负载L-脯酰胺催化剂的催化性能。发现：催化基团邻近主链时（间隔臂较短）比远离主链者给出了更好的催化效果，由三级酰胺单元构成的拟肽主链可明显增强不对称诱导效应，提高对映选择性。在本体反应条件下，得率达到90%以上，反式加成产物占优（anti/syn ~80:20），ee值大于90%。产物分离简单，催化剂循环使用5次效果基本保持不变。3）设计、合成了侧链含有L-脯酰胺催化基团的聚（2-噁唑啉）两亲均聚物和共聚物。动态光散射和透射电镜观察证实，两亲均聚物在水溶液中自组装形成直径为10-30 nm的胶束型聚集体。有趣的是，这种纳米粒子不具有明确的核-壳结构，其大部分催化单元包埋在疏水内核。作为纳米反应器，此类均聚物胶束可有效催化Aldol反应，立体选择性高于无规共聚物和嵌段共聚物体系，dr和ee值分别达到83%和75%。综述所述，本项目开发了新型的聚合物负载有机催化剂，取得的成果为探索有机催化体系的仿酶设计提供了新的思路。