Date of Award
Doctor of Philosophy
David M. Jenkins
Michael D. Best, Craig E. Barnes, Siris O. Laursen
Aziridines, the nitrogen analog of epoxides, are an important class of compounds. They are present in many biologically active compounds having antibacterial and antitumor properties. Along with biological significance, it can also be considered as a synthetic tool for various functional group transformations. Being an important functional group we focused on the development of synthetic methodology using alkenes as substrates and organic azides as the nitrene source [C2 (carbon2)+ N1 (nitrogen1) addition reaction].
For the potential use as an aziridination catalyst a macrocyclic N-heterocyclic tetracarbene (NHC) ligand system was developed. First, the neutral NHC ligand was used to synthesize ruthenium(II) complex that was found catalytically inactive for aziridination. Due to the limitations such as poor solubility, the second generation, borate-containing dianionic NHC ligand was developed. Using this 18-atom ring ligand cobalt(II) and manganese(III) and iron(III) complexes with neutral charge were synthesized.
Further, iron(III) complex was reduced to form the square planar iron(II) neutral complex. This complex successfully performed fully aliphatic aziridination involving functional group tolerance. In order to check the versatility of the catalyst it was also tested with aliphatic alkenes and aryl azide, which resulted in high yields of corresponding aziridines. Finally, the catalyst successfully performed intramolecular C2 + N1 aziridination to form five- and six-membered bicyclic aziridines.
Another aspect of the project was to investigate the mechanism of the catalytic C2 + N1 aziridination reaction for this tetracarbene system. We were able to isolate an iron(IV) tetrazene complex that support the argument of a reactive iron(IV) imide as an intermediate in the catalytic cycle. In order to explore the reaction pathway from imide to aziridine we carried out reactions with p-tolyl azide in presence of cis- and trans- alkenes that formed the syn- and anti- aziridines. This observation suggested the formation of radical intermediate, which was also supported by DFT [density functional theory] calculations.
Lastly, we also synthesized N-carbamate aziridines from carbamate azides with boc-, fmoc-, and cbz- groups and aliphatic alkenes. Deprotection and nuclephilic ring opening reactions on these carbamate aziridines will be carried out in future.
Chandrachud, Preeti Pradip, "Catalytic Aziridination with a Borate-containing N-Heterocyclic Tetracarbene Iron Complex. " PhD diss., University of Tennessee, 2016.