The formation of iminyl radicals from a range of precursors, including hydrazone imines and oxime ethers, under FVP conditions is well documented in the literature.1 Once formed, the iminyl radical can undergo cyclisation onto various aromatic ring systems including phenyl rings, thiophenes and furans to form new fused aromatics.2 The aim of this thesis was to expand the scope of cyclisation of iminyl radical onto pyrrole-type rings and 2-azole rings, generating novel heterocyclic cores via pyrolysis of the corresponding oxime ether precursors. In addition, the cyclisation of iminyl radicals onto C-C double bonds was investigated and afforded isoquinolines shown in Scheme II, providing a new way to synthesise these heterocyclic cores. Mechanistic predictions were supported by DFT calculations in which the thermodynamics and kinetics of the systems were established and the products of iminyl cyclisation reactions were characterised using a range of 2D NMR experiments.

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.