Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Chemistry

Supervisor

Pagenkopf, Brian L.

Abstract

Donor-acceptor (D-A) cyclobutanes are a well recognized building block in synthetic organic chemistry thanks to their unique reactivity. A variety of synthetic methodologies such as cycloaddition, rearrangement, and ring-opening addition of D-A cyclobutanes have been reported. Among them, the rearrangement reactions of D-A cyclobutanes have attracted less interest compared with other methodologies as they too often require extreme reaction conditions. To further explore the rearrangement reactions of D-A cyclobutanes, in this work a ring expansion rearrangement reaction of D-A cyclobutanes analogous to the Cloke–Wilson reaction of cyclopropanes was examined. By exploiting the solvent effect in a Brønsted acid system, we successfully acquired the target lactone products in moderate yield (49–65%).

The current work also demonstrated that alkoxy-activated cyclobutanes could undergo a ring-opening and nucleophilic addition to generate nucleophilic substituted products under mild condition with good yield (58–98%). These products are good scaffolds to access cyclic compounds that are commonly found in natural products.

Summary for Lay Audience

In modern society, the pharmaceutical and healthcare industries have improved the quality of public health and individual wellbeing. Organic synthesis is one basic area of chemistry that contributes to drug discovery and development. Many organic chemists work to find more efficient and cost-effective synthetic methods to make pharmacophores and drug related molecules.

In the cyclobutane molecule, the carbon bond angles are highly distorted from normal, and as a result cyclobutane becomes reactive. Putting electron-donating and electron-accepting (DA) functional groups on adjacent carbons further increases reactivity, but in a controlled way that chemists can harness to make new molecules. Various strategies have been developed to transform D-A cyclobutanes into more valuable materials.

Biologically active molecules containing an oxygen atom within a cyclic structure, known as a heterocycle, are common in nature. My research focuses on accessing oxygen-containing heterocycles from D-A cyclobutane as starting materials. Lactone is one of the most common oxygen-containing heterocycles found in drugs and medicinal intermediates. In this thesis, we study the intramolecular oxygen transfer of D-A cyclobutane to access δ-lactone compounds.

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