Date of Degree

5-2019

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor

Stephen Philip Fearnley

Committee Members

Adam Profit

Elise Champeil

Subject Categories

Organic Chemistry

Keywords

Intramolecular Diels-Alder cyclization, oxazolone, intramolecular Friedel-Crafts cyclization, Fischer indole synthesis

Abstract

The synthesis of heterocyclic compounds and their incorporation into total synthesis strategies are described. Three synthetic methodologies toward substituted indoles, isochromans, and fused multi-ring oxazolidinones have been examined. With the progress that has been made, further investigations will hopefully carry the concept to completion.

Chapter I is an introductory examination of the varied types and systematic nomenclature of heterocyclic structures, including common names. This continues on to their commercial and industrial usage, and their great importance in biological systems and natural product chemistry. Finally, examples of heterocycles in fused-ring natural products and examples of historical and/or commercial value are examined by heteroatom-containing ring structure.

Chapter II reports upon historical indole synthesis methodology, and schemes of novel strategies towards Fischer indole precursors and eventual indolization. The methodology consists of investigations into the viability of the condensation of quinone mono ketals (QMK) and non-enolizable alkyl hydrazines (tert-butylhydrazine and tert-butylcarbazate), in two methodological series, to yield diazenes. This lead towards an initial foray into the Fischer cyclization of resultant diazene products emanating from the condensation of QMKs and enolizable alkyl hydrazines. The second permutation consists of the condensation reaction of nitrosobenzenes and alkylamines, once again towards Fischer indolization reactions.

Chapter III delves into the Lewis acid-promoted, Friedel-Crafts cyclization/ intramolecular C-glycosylation of trimethylsilylbenzyl ether-tethered oxolanes and oxanes compounds, including one glucosyl example. The methodology only sporadically progresses to product when the TMS directing group is not present, and its necessity was proved through previously-executed deuterium experiments. Exhaustive proofs of structures are explored through spectroscopic techniques.

Chapter IV examines the incorporation of 2-oxazolone-tethered terminal conjugated dienes as means towards tricyclic cycloadducts through intramolecular Diels-Alder reactions. The resulting common core precursors are the focus of a divergent synthetic strategy. From this approach, divergent families of natural products can be synthesized from the common precursor through direct incorporation of the tricyclic intermediate, or through a scission-rearrangement process directed towards other compound families with entirely different skeletal ring structures.

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