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

在化学系化学催化项目的支持下，田纳西大学的大卫詹金斯和康斯坦丁诺斯·沃吉亚齐斯的合作团队将研究形成环氧化物和氧氮杂环丙烷的催化反应。环氧化合物和氧氮杂环丙烷是合成化学中广泛使用的张力三元环。催化剂将基于铁或其他第一行过渡金属，因为这些金属价格便宜且地球资源丰富。金属将具有手性配体（即具有手性），使得在反应期间仅形成产物的一种对映异构体（镜像形式）。选择性地形成环氧化物或氧氮丙啶靶标的单一对映异构体对于许多生物学和医学应用是关键的。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，该团队将使用计算化学来更好地理解反应机理，并协助提高催化转化率，并可能帮助指导手性配体设计。该项目旨在开发用于此类烯烃环氧化/氮杂环丙烷化反应的最具对映选择性的铁催化剂。如果成功的话，这种铁基催化剂将对合成化学界非常有价值。该团队还将为研究生培训开展暑期项目，包括面对面的国际交流项目和为开始博士研究的学生提供的在线研究生预备培训。田纳西大学的大卫詹金斯和康斯坦丁诺斯·沃吉亚齐斯的合作团队将研究形成环氧化物和氧氮杂环丙烷的催化反应。该项目的基本目标是开发有效的手性催化环氧化和氧氮杂环丙烷化反应，这些反应可用于各种前手性底物，如烯烃和亚胺。 特别是，他们将开发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烯烃反应产生手性环氧化物。目前，没有对映选择性铁催化剂与这种试剂组合反应以得到对映体富集的环氧化物。为了实现这些目标，Jenkins团队将开发新的合成方法来生成手性NHC大环化合物，这些大环化合物在结构上类似于更知名的卟啉。这些D2-对称大环具有模块化的手性口袋，可以通过与一类手性二咪唑配体配位来潜在地进行调节。Vogiatzis小组将领导计算研究部分，对不同的NHC-配体支架进行对映选择性催化的虚拟预筛选。 该团队将致力于通过这种理论和实验相结合的方法来阐明催化反应的机制。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.