Date of Award
Doctor of Philosophy
Richard C. Larock
George A. Kraus
The six chapters of this dissertation exemplify the application of aryne chemistry in medicinally-relevant, nitrogen-containing heterocycle synthesis. The arynes discussed in this dissertation are generated from Kobayashi's aryne precursors that leads to novel synthetic methodology. Chapter 1 begins by detailing the overall organization of this dissertation and follows with a brief review of arynes, which provides the reader with a general understanding of this highly reactive intermediate and its application in various organic transformations.
Chapter 2 describes the chemical reactivity of 2,3-pyridyne in the presence of amines. We have found that amines attack the 2-position of 2,3-pyridyne exclusively to afford the corresponding 2-aminopyridines. In addition, a series of benzonaphthyridinones have been synthesized by reacting 2,3-pyridyne with o-aminobenzoates.
Chapter 3 describes a project involving the reaction of beta-lactams and arynes. In this process, the aryne inserts into carbon-nitrogen bond of the beta-lactam to form a 2,3-dihydroquinolin-4-one, which subsequently reacts with another molecule of aryne to form an acridone by extrusion of a molecule of ethylene. 2,3-Dihydroquinolin-4-ones react under the same reaction conditions to afford acridones. This is the first example of ethylene extrusion in aryne chemistry.
Chapter 4 describes a rapid and efficient synthesis of 2H-indazoles using a [3 + 2] dipolar cycloaddition of sydnones and arynes. A series of 2H-indazoles have been prepared in good to excellent yields using this protocol, and subsequent Pd-catalyzed coupling reactions can be applied to the halogenated products to generate a structurally diverse library of indazoles. This methodology has been highlighted in Synfacts.
Chapter 5 details a methodology for synthesizing 2H-isoindoles and 9,10-dihydro-9,10-epiminoanthracenes from arynes and münchnones. 2H-Isoindoles have been generated from arynes and münchnones by a [3 + 2] dipolar cycloaddition process under very mild reaction conditions. Due to the high reactivity of 2H-isoindoles with arynes, 9,10-dihydro-9,10-epiminoanthracenes are ultimately formed in the presence of arynes in good to excellent yields.
Lastly, Chapter 6 makes some general conclusions about the previous chapters.
Fang, Yuesi, "Synthesis of Bioactive Nitrogen-Containing Heterocycles via Aryne Methodologies" (2012). Graduate Theses and Dissertations. 12674.