Reed, Hayley2021-02-232021-02-232020https://udspace.udel.edu/handle/19716/28778This dissertation focuses on the development of new methodologies for aromatic functionalization and heterocycle synthesis via the excision of the N–O bond in aniline N-oxides. Chapter 1 serves as an introduction to aromatic functionalization methods with a focus on those achieved through exploiting the cleavage of N–O bonds. Chapters 2 and 5 focus on the use of aniline N-oxides to prepare halogenated anilines and aryl sulfoxides. Chapters 3 and 4 concentrate on the synthesis of tetrahydroquinolines and indoles via aniline N-oxides. ☐ Chapter 2 describes a metal-free method of preparing halogenated anilines from aniline N-oxides via activation of N-alkyl-N-methylaniline N-oxides with thionyl halides. A variety of aromatic substituents and substitution patterns as well as differentially N-substituted aniline N-oxides were tolerated. Treatment of aniline N-oxides with thionyl bromide selectively produced para-bromoanilines; treatment of aniline N-oxides with thionyl chloride preferentially synthesized ortho-chloroanilines. Excitingly, this methodology does not require Lewis acids, exotic reagents, or activation of halogen sources. Preliminary mechanistic experiments suggest that para-halogenation occurs via a nucleophilic addition mechanism and ortho-halogenation occurs via a [3,3]-sigmatropic rearrangement. ☐ Chapter 3 describes Polonovski-Povarov cyclizations to prepare tetrahydroquinoline scaffolds from aniline N-oxides and N-vinylpyrrolidone and 2-phenylpropene. Metal-free conditions to achieve these transformations are also disclosed. Derivatives of synthesized tetrahydroquinoline scaffolds were prepared. Preliminary mechanistic investigations into both transformations indicate that the cyclization can occur via a concerted or stepwise Povarov reaction mechanism. ☐ Chapter 4 describes efforts towards using aniline N-oxides and β-ketoacyl chlorides to prepare 2-substituted indoles, specifically 2-reverse prenylated indoles. The use of β-ketoacyl chlorides would allow for a versatile methodology for preparing diverse 2-substiuted indoles beyond 2-reverse prenylated indoles. Preliminary investigations have not resulted in the synthesis of the desired indole products; however, further optimization of this methodology is ongoing. ☐ Chapter 5 describes efforts towards preparing aryl sulfoxides from aniline N-oxides and alkyldisulfanium salts. The use of alkyldisulfanium salts to activate aniline N-oxides would provide a metal-free method of preparing differentially substituted sulfoxides. Preliminary efforts have prepared few examples of aryl sulfoxides in low yields. No further optimization of this reaction is planned.Aromatic functionalizationHeterocycle synthesisAniline N-OxidesThesis1238100575https://doi.org/10.58088/8mq6-18332020-10-13en