CAS: Chiral Epoxidation and Oxaziridination Catalysis with First-row Transition Metals

CAS：第一行过渡金属的手性环氧化和氧氮丙啶化催化

• 批准号: 2154697
• 负责人: David Jenkins
• 金额: $ 62.5万
• 依托单位: University of Tennessee Knoxville
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154697&HistoricalAwards=false
• 关键词: CAS; Chiral; Epoxidation; Oxaziridination; Catalysis

With the support of the Chemical Catalysis program in the Division of Chemistry, the collaborative team of David Jenkins and Konstantinos Vogiatzis of the University of Tennessee will study catalytic reactions for the formation of epoxides and oxaziridines. Epoxides and oxaziridines are strained three-membered rings that are widely employed in synthetic chemistry. The catalysts will be based on iron or other first-row transition metals since these are inexpensive and earth abundant. The metals will have chiral ligands (i.e. possessing handedness) so that only one enantiomer (mirror-image form) of the product is formed during the reaction. Selectively forming a single enantiomer of the epoxide or oxaziridine target is critical for many biological and medicinal applications. The synthesis of the ligands is modular, so many different sized chiral pockets can be prepared. To accelerate the research, the team will use computational chemistry to better understand reaction mechanism and assist in improving catalytic turnover and potentially help guide chiral ligand design. This project aims to develop among the most enantioselective iron catalysts for such alkene epoxidation/aziridination reactions across a broad class of reagents. If successful, such iron-based catalyst will be highly valuable for the synthetic chemistry community. The team will also conduct summer programs for graduate student training including in-person international exchange programs and online graduate preparatory training for students beginning their PhD studies.The collaborative team of David Jenkins and Konstantinos Vogiatzis of the University of Tennessee will study catalytic reactions for the formation of epoxides and oxaziridines. Their fundamental aspiration of this project is to develop effective chiral catalytic epoxidation and oxaziridination reactions that work with a wide variety of prochiral substrates such as olefins and imines. In particular, they will develop catalysts based upon iron and other first-row transition metals that react with an oxidant and aliphatic alkenes to produce chiral epoxides. At present, there are no enantioselective iron catalysts that react with this combination of reagents to give enantio-enriched epoxide. To achieve these goals the Jenkins group will develop new synthetic methodology to generate chiral NHC macrocycles that are structurally analogous to the more well-known porphyrins. These D2-symmetric macrocycles have modular chiral pockets that can potentially be tuned through coordination with a class of chiral diimidazole ligands. The Vogiatzis group will lead the computational research component with regard to a virtual pre-screening of different NHC-ligand scaffolds for enantioselective catalysis. The team will work to elucidate the the mechanism of the catalytic reaction through this combined theoretical and experimental approach.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学催化计划的支持下，田纳西大学的David Jenkins和Konstantinos Vogiatzis的合作团队将研究催化反应，以形成环氧化物和奥沙爱速胺。环氧化物和阿沙素是三元环，这些环被广泛用于合成化学。催化剂将基于铁或其他第一行转换金属，因为它们廉价而丰富。这些金属将具有手性配体（即拥有手的），因此在反应过程中只形成了产物的一种对映异构体（镜像形式）。有选择地形成环氧化物或黄氧胺靶标的单个对映异构体对于许多生物学和药用应用至关重要。配体的合成是模块化的，因此可以制备许多不同大小的手性口袋。为了加速研究，团队将使用计算化学来更好地理解反应机制，并有助于改善催化转移，并可能有助于指导手性配体设计。该项目旨在开发以烯烃环氧化/氮化反应的大量试剂反应的最大选择性铁催化剂之一。如果成功的话，这种基于铁的催化剂对于合成化学界将非常有价值。该团队还将为研究生培训进行夏季课程，包括面对面的国际交流计划和开始他们的博士学位研究的学生的在线研究生预备培训。他们对该项目的基本觉得是开发有效的手性催化环氧化和黄孢子反应，这些反应与多种烯烃和亚胺等多种培养基底物一起起作用。 特别是，它们将基于铁和其他第一行过渡金属的催化剂，这些金属与氧化剂和脂肪族烷烃反应以产生手性环氧化物。目前，没有对映选择性铁催化剂与这种试剂的组合反应，从而产生富含对映的环氧化物。为了实现这些目标，詹金斯组将开发新的合成方法论，以产生手性NHC大环在结构上类似于更知名的卟啉。这些D2对称的大环具有模块化手性袋，可以通过与一类手性二咪唑配体配位来调节。 Vogiatzis组将领导计算研究组成部分，以进行对映选择性催化的不同NHC-配体支架的虚拟预筛查。 该团队将通过这种合并的理论和实验方法来阐明催化反应的机制。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响评估标准，认为值得通过评估来获得支持。