Enantioselective Epoxidation Catalysts on Helical Polymer Supports

摘要提案标题：螺旋聚合物载体上的对映选择性环氧化催化剂提案编号：CTS-0626143主要研究者： 大卫A. Bruce机构： 克莱姆森大学分析（决策依据）：手性精细化学品的有效合成对先进医药和农业产品的开发和生产至关重要。 目前，大多数手性化合物是通过均相不对称催化或非手性合成与手性分离相结合来制备的。尽管均相催化历来提供最高水平的对映选择性，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，这种活性的范围是一个强大的非均相催化剂的合成和建模，表现出高对映体选择性的非官能化烯烃的环氧化。具体地，螺旋聚合物载体将用于使salen金属络合物多相化，其是高度选择性的不对称的均相环氧化催化剂。 螺旋聚合物载体是胺官能化的亚苯基亚乙炔基低聚物，当与廉价的不对称结构导向剂（例如，- 蒎烯）形成螺旋二级结构，其先前已在吸附实验中显示出手性选择性。 在不对称螺旋聚合物的外部上的胺官能团将用作salen金属络合物的双齿配体。与遭受降低的对映体选择性和金属浸出的现有聚合物负载的催化剂不同，这些催化剂从不对称聚合物载体获得它们的手性，并且活性金属物质通过两个官能团结合到载体上，因此降低了金属浸出的程度。所提出的催化剂合成方法的另一个优点是分子模拟研究将用于指导最佳催化剂材料的设计。影响聚合物二级结构形成和反应物吸附的分子相互作用将使用分子动力学（MD）和副本交换MD技术，采用修改后的GROMACS模拟代码，我们已经优化了这些材料的研究。手性环氧化物是许多医药和不对称精细化学品的重要原料，不对称聚合物负载的环氧化催化剂具有高的对映选择性和催化剂的重复使用性，但目前利用非均相催化剂制备手性环氧化物的方法还很少。通过模型化和实验相结合的方法，本研究将有助于开发新型的对映选择性环氧化催化剂，从而降低医药和不对称精细化学品的生产成本。该研究计划还旨在让研究生和本科生参与研究的各个阶段。 这项研究工作的一个特别的教育优势是，每个学生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于新型催化剂材料的合成。 最终的教育成果将是积极性很高的本科生，他们希望受到启发，在研究生阶段寻找机会，博士研究人员将能够在工业或学术界领导催化或建模的研究工作。 因此，这些努力将导致新的催化材料和受过高等教育的毕业生，他们将能够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.