Degree Type

Dissertation

Date of Award

2012

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Richard C. Larock

Second Advisor

George A. Kraus

Abstract

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.

Copyright Owner

Yuesi Fang

Language

en

File Format

application/pdf

File Size

242 pages

Included in

Chemistry Commons

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