The Synthesis of Heterocycles and Carbocycles and Work Towards Kainic Acid
Abstract
This thesis focuses on the synthesis of a variety of heterocycles and carbocycles such as pyrrolidines, dihydrofurans, dihydropyrroles, cyclopentenes, and 2,5-dihydrooxepines. Traditional synthetic methods are discussed first, followed by the manipulation of donor-acceptor cyclopropanes towards the above-mentioned compounds. This leads to a discussion about an important pyrrolidine-containing natural product known as kainic acid. Kainic acid has been studied in the neuroscience field for its biological properties which have led to a better understanding of common human neurological disorders like epilepsy, Huntington’s disease and the after-effects of strokes.
Chapter two focuses on a common rearrangement of donor-acceptor cyclopropanes known as the Cloke-Wilson reaction. Without isolating the desired cyclopropane, two modes of reactivity were observed which depended solely on the choice of starting reagent. The first was the traditional Cloke-Wilson rearrangement generating dihydrofurans and the second was a vinylogous variant forming 2,5-dihydrooxepines. It was discovered that with careful choice of Lewis acid or transition metal catalysts, each of the obtained compounds can be manipulated to other dihydrofuran derivatives or dihydropyrrole heterocycles. One of the dihydropyrrole compounds obtained was deemed as a viable synthetic precursor towards kainic acid.
Chapter three describes the synthetic efforts towards kainic acid utilizing the methodology from chapter two. The difficulties towards this natural molecule will be presented with the major issue resulting from stereochemical constraints. This resulted in the successful synthesis of β-allokainic acid which is one of the less active isomers of naturally occurring kainic acid.
Chapter four discloses a single-step manipulation of the dihydrofurans synthesized via Cloke-Wilson rearrangement to their corresponding cyclopentenes. Extensive screening of Lewis acids and solvents provided insights into the possible mechanism of this reaction.