Date of Award

3-1-2014

Document Type

Dissertation

Degree Name

Ph.D.

Organizational Unit

College of Natual Science and Mathematics

First Advisor

Andrei G. Kutateladze

Second Advisor

Gareth R. Eaton

Third Advisor

Martin Margittai

Fourth Advisor

Bryan J. Cowen

Fifth Advisor

Joseph Angleson

Keywords

Cycloaddition, Oxametathesis, Photochemistry, Polyheterocycles

Abstract

Photoassisted diversity-oriented synthesis holds great promise in its ability to provide rapid access to complex and diverse molecular scaffolds. As it stands, while photochemical techniques have this potential, their implementation in the field of synthetic organic chemistry is very limited. The main goal of this project was to utilize photochemically assisted techniques in the synthesis of a variety of novel polyheterocycles.

Initially, we explored the how the strain installed in these polycycles could be harnessed to trigger cationic rearrangements in the framework of the system. This was achieved via the high yield and rapid assembly of a highly strained system containing two oxetanes. This bis-oxetane was derived from a compound containing carbonyl groups endo- to two respective bicyclic olefins which was assembled via a simple Diels-Alder step. The oxetanes were formed in a Paternò-Büchi reaction via excited-state chemistry. The protolytic ring-opening of this bis-oxetane compound afforded two highly unusual polycyclic products that both result from rather complex mechanisms which are proposed in this work. In addition, we were able to elaborate on this rapid Diels-Alder assembly motif by designing a double-tandem [4+2][2+2][4+2][2+2] synthetic sequence which culminates in a complex scaffold containing an oxetane. When subjected to acidolysis, this oxetane affords a complex polycycle with rigidly held pendants rich in heteroatoms.

We then intended to study how a bicyclic olefin which also possessed endo-carbonyl groups would perform during irradiation when the length of the tether to the bicyclic system was lengthened. This lengthened tether allowed flexibility in the regiochemistry of the Paternò-Büchi cycloaddition. The regiochemistry was also able to be controlled by the introduction of a methyl group in the tether. The protolytic opening of the two different oxetanes gave polyheterocyclic products with completely different scaffolds that both demonstrate a great increase in complexity of structure relative to the quite simple starting materials.

In a departure from Paternò-Büchi, our next design strategies focused on the photo-generation of azaxylylenes via excited-state intramolecular proton transfer. We tethered these azaxylylenes to unsaturated pendants in the hopes that the short-lived intermediate would undergo cycloaddition with these pendants. In this endeavor, we were able to observe both [4+4] and [4+2] cycloadditions, depending on the type of pendant used. We were able to diversify this system by utilizing both carbonyls and imines as the proton abstraction agents, by using thiophene and furan as the unsaturated pendant, and by tethering the pendant to the carbonyl “half” and the aniline “half” of the photoprecursor—demonstrating the tolerance that this system has for a large range of modifications.

With the optimization of these methodologies, we aim to pave the way for the incorporation of photochemistry into the toolbox of synthetic chemists by demonstrating the molecular diversity that these techniques allow.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

Teresa M. Cowger

Provenance

Received from ProQuest

File Format

application/pdf

Language

en

File Size

176 p.

Discipline

Chemistry

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