Enantioselective Epoxidation Catalysts on Helical Polymer Supports

摘要提案题目：螺旋聚合物载体上的对映选择性环氧化催化剂提案号：ccs - 0626145首席研究员：David A. bruce机构：克莱姆森大学分析（决策依据）：手性精细化学品的高效合成对先进药品和农产品的开发和生产至关重要。目前，大多数手性化学物质是通过均相不对称催化或非手性合成结合手性分离制备的。虽然均相催化在历史上提供了最高水平的对映体选择性，但多相催化具有催化剂重复使用和简化产物纯化的优点。因此，该活性的范围是合成和模拟一种具有高对映选择性的非官能化烯烃环氧化的坚固的多相催化剂。具体来说，螺旋聚合物载体将用于异构化salen金属配合物，这是一种高选择性的不对称，均相环氧化催化剂。螺旋聚合物载体是胺功能化的苯乙烯低聚物，当与廉价的不对称结构定向剂（如-蒎烯）结合时，形成螺旋二级结构，在吸附实验中已被证明具有手性选择性。在不对称螺旋聚合物表面的胺官能团将被用作双齿配体的salen金属配合物。与先前聚合物载体催化剂的对映选择性降低和金属浸出不同，这些催化剂的手性来自于不对称的聚合物载体，活性金属通过两个官能团与载体结合，从而降低了金属浸出的程度。提出的催化剂合成方法的另一个优点是，分子建模研究将用于指导最佳催化剂材料的设计。分子相互作用对聚合物二级结构形成和反应物吸附的影响将使用分子动力学（MD）和复制交换MD技术进行研究，这些技术采用了改进版本的GROMACS模拟代码，我们已经为这些材料的研究进行了优化。所提出的不对称聚合物负载的环氧化催化剂为手性环氧化物的生产提供了高对映选择性和易于重复使用的可能性，这是许多药物和不对称精细化学品的重要组成部分。目前，利用多相催化剂制备手性产物的方法很少。随着模型和实验的结合，这项研究将导致新的对映选择性环氧化催化剂的开发，这将有助于降低生产药物和不对称精细化学品的成本。该研究计划的设计还包括研究生和本科生参与研究的各个阶段。这项研究的一个特别的教育优势是，每个学生都将获得分子建模的经验，然后有机会将这些研究的结果应用到新型催化剂材料的合成中。最终的教育成果将是高度激励的本科生，他们将有望被激励去寻找研究生水平的机会，以及能够在工业界或学术界领导催化或建模研究工作的博士研究人员。因此，这些努力将带来新的催化材料和高学历的毕业生，他们将有能力领导科学和工程的进一步发展。

AbstractProposal Title: Enantioselective Epoxidation Catalysts on Helical Polymer Supports Proposal Number: CTS-0626143Principal Investigator: David A. BruceInstitution: Clemson UniversityAnalysis (rationale for decision):The efficient synthesis of chiral fine chemicals is essential to the development and production of advanced pharmaceutical and agricultural products. Currently, most chiral chemicals are produced via homogeneous asymmetric catalysis or achiral synthesis coupled with chiral separations. Though homogeneous catalysis has historically provided the highest levels of enantioselectivity, heterogeneous catalysis offers the advantages of catalyst reuse and simplified product purification. Thus, the purview of this activity is the synthesis and modeling of a robust heterogeneous catalyst that exhibits high enantioselectivity for the epoxidation of unfunctionalized olefins. Specifically, helical polymer supports will be used to heterogenize salen metal complexes, which are highly selective asymmetric, homogeneous epoxidation catalysts. The helical polymer supports are amine functionalized phenylene ethynylene oligomers that when combined with inexpensive asymmetric structure directing agents (e.g., -pinene) form helical secondary structures, which have been previously shown to exhibit chiral selectivity in adsorption experiments. The amine functional groups on the exterior of the asymmetric helical polymers will be used as bidentate ligands for the salen metal complexes. Unlike prior polymer supported catalysts, which suffered from reduced enantioselectivity and metal leaching, these catalysts derive their chirality from the asymmetric polymer support and the active metal species are bound via two functional groups to the support, thus, reducing the extent of metal leaching. A further advantage of the proposed catalyst synthesis approach is that molecular modeling studies will be used to guide the design of the optimal catalyst material. The molecular interactions affecting polymer secondary structure formation and reactant adsorption will be studied using molecular dynamics (MD) and replica exchange MD techniques that employ a modified version of the GROMACS simulation code, which we have optimized for studies of these materials. The proposed asymmetric polymer-supported epoxidation catalysts offer the possibility of high enantioselectivity and easy catalyst reuse for the production of chiral epoxides, which are important building blocks for many pharmaceuticals and asymmetric fine chemicals.Currently, methods to produce chiral products using heterogeneous catalysts are few in number. With the melding of modeling and experimentation, this research will lead to the development of new enantioselective epoxidation catalysts that will help to reduce the cost of producing pharmaceuticals and asymmetric fine chemicals. The research program has also been designed to involve graduate and undergraduate students in all phases of the research. A particular educational advantage of this research effort is that each student will gain experience in molecular modeling and then have the opportunity to apply the results from those studies to the synthesis of novel catalyst materials. The ultimate educational outcomes will be highly motivated undergraduates who will hopefully be inspired to seek out opportunities at the graduate level and doctoral researchers who will be capable of leading a research effort in catalysis or modeling in either industry or academia. Thus, these efforts will lead to both novel catalytic materials and highly educated graduates who will be capable of leading further advances in science and engineering.