Synthetic applications of functionalized aziridines

This thesis contains three parts of research, all of which are focused on utilizing aziridines as the intermediates to synthesize valuable building blocks or bioactive structures. The aziridine functionality, a three-membered ring structure containing a nitrogen atom, is widely used in synthesis for chemical bond elaborations and functional group transformations. The most important synthetic application of aziridines is their ring opening reactions which take advantage of strain in the three-membered ring. Other special properties such as oxidative stability or weak basicity have seldom been considered as the rationale for synthetic methodology development or utilized in synthetic route design.;The second part of this thesis deals with an application of the above methodology towards the natural product ficellomycin. Ficellomycin is a naturally occurring antibiotic which shows in vivo antibacterial activity. Due to its rare chemical structure, no successful total synthesis has been reported. We noticed that our aziridine cyclization methodology can be applied to the synthesis of ficellomycin. In this thesis, two synthetic approaches were developed to construct the core structure of ficellomycin. The control of the relative stereochemistry provides an opportunity to synthesize the diastereomeric analogs of ficellomycin.;In the third part of the thesis, synthesis of allyl amines from 2-ketoaziridines has been studied. Allyl amine structures are often found in natural products and pharmaceuticals. The hydrazinolysis of 2-ketoaziridines were found to afford allyl amines and pyrazoles. The reaction condition was optimized. The electronic and steric effects from the substituents were studied. A variety of 2-ketoaziridines were transformed into diversely substituted linear or cyclic allyl amines in good yields using this methodology.;In the first part of this thesis, the oxidative stability of aziridines was utilized to carry out a sequence of cyclization and aziridine-opening transformations. The process provides straightforward synthetic entries into a range of larger heterocyclic structures (such as five-membered ring pyrrolidine or six-membered ring piperidine) which are often found in the bioactive natural products or pharmaceuticals. This methodology is of significance in term of generating libraries of the nitrogen heterocycles. The broad scope of substrates used in this research demonstrates the potential value of this methodology.