Direct arylation of 2-pyrones, coumarins, 2-pyridinones and 2-quinolones

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Nolan, Marie-Therese
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University College Cork
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Direct arylation via C-H activation displays a number of advantages over traditional (Suzuki-Miyaura, Stille, etc.) coupling reactions. The 2-pyrone, coumarin, 2-pyridinone and 2-quinolone moieties are prevalent in numerous compounds which exhibit biological activity. In addition, due to the varied chemistry that these compounds display, they represent an excellent substrate scope to challenge any methodology. Chapter 1 involves a discussion of the prevalence of 2-pyrones and 2-pyridinones and their corresponding analogues in naturally occurring biologically active compounds. We review their chemical and biosynthesis, as well further elaboration of the core compounds. The mechanism of traditional cross-coupling reactions proceeding via palladium catalysis, including the advances made over the past few decades in C-H bond functionalisation through direct arylation and double C-H activation is also discussed. Chapter 2 incorporates a description of two new strategies for the selective intramolecular direct arylation of a wide range of 2-pyrones and 2-pyridinones via palladium catalysis, allowing access to novel tricyclic motifs in high yields. We then present our investigations which led to the successful intermolecular direct arylation of coumarins. This is followed by a discussion on the development of two sets of conditions enabling selective intramolecular double C-H activation of both the 2-pyrone and coumarin motif. The potential pathways and mechanisms for each of the methodologies presented are also discussed. Chapter 3 contains a description of the experimental studies and synthetic procedures that were performed in the development of our successful intramolecular and intermolecular direct arylation and double C-H activation reactions. Key analytical and spectroscopic properties of the compounds studied are also reported herein.
2-Pyrones , Direct arylation
Nolan, M-T. 2018. Direct arylation of 2-pyrones, coumarins, 2-pyridinones and 2-quinolones. PhD Thesis, University College Cork.