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

University Of Tennessee Knoxville, Knoxville TN

Investigators

Abstract

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.