Abstract

The first project in this dissertation presents a simplified and efficient protocol for synthesizing pyrrolines through 5-exo iminyl radical cyclizations. The microwave irradiation of O-Phenyloximes tethered to alkenes causes N-O homolysis resulting in iminyl radical generation, which subsequently undergoes 5-exo-trig cyclizations furnishing pyrrolines. This eliminates the need for toxic radical initiators (AIBN, benzoyl peroxide), propagating agents (Bu3SnH, (Me3Si)3SiH), and expensive catalysts or single-electron transfer (SET) cycles. We explored the scope of diverse traps and substrates for iminyl radical cyclizations. The iminyl radical cyclizations formed versatile pyrrolines with moderate to excellent yields. The diastereoselectivity also ranged from low to high. Moreover, these versatile pyrrolines were further transformed via various reactions, such as hydrogenation, allylation, dihydroxylation, and cross-metathesis. The second part of this project extends the scope of the non-redox iminyl-radical based approach to γ-C(sp3)−H ketone activation. The sequence of N-O homolysis triggered by microwave irradiation of O-phenyloximes, 1,5-hydrogen atom transfer (HAT), trapping of the radical intermediate, and in situ imine hydrolysis, ultimately leads to the formal γ-C–H functionalization of ketones. We achieved both C-O and C-C bond formation by using diverse O-phenyloxime substrates. This work's notable achievement was accomplishing γ-C–H activation of 1o carbon atoms, a feat that has not been attained using SET-based iminyl radical chemistry. The third part of this dissertation focuses on the influence that dehydroamino acids have on secondary structures. This project describes the synthesis of incipient 310 helical tetrapeptides containing dehydroamino acids. A bulky dehydroethylnorvaline-containing tetrapeptide was synthesized. Based on our published data, we speculated that dehydroethylnorvaline might increase peptide proteolytic stability.

Degree

PhD

College and Department

Physical and Mathematical Sciences; Chemistry and Biochemistry

Rights

https://lib.byu.edu/about/copyright/

Date Submitted

2023-08-14

Document Type

Dissertation

Handle

http://hdl.lib.byu.edu/1877/etd12940

Keywords

Iminyl radicals, Pyrrolines, Microwave irradiation, C-H activation, 1, 5-Hydrogen atom transfer (HAT), bulky dehydroamino acids

Language

english

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