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Type: Thesis
Title: Towards the synthesis of the monoterpene furanoid oxides via the ozonolysis of bicyclic bridged 1,2-Dioxines.
Author: Cain, Nicole Marie
Issue Date: 2011
School/Discipline: School of Agriculture, Food and Wine
Abstract: 1,2-Dioxines, also known as endoperoxides are a specific type of cyclic peroxide, characterised by an unsaturated six-membered peroxide ring. They are abundant in nature and have been isolated from many natural products and have been shown to exhibit a wide spectrum of biological roles. Ozonolysis is a well established method for the oxidative cleavage of alkenes, although examples involving 1,2-dioxines are extremely rare. The furanoid and anhydrofuran linalool oxides have been established as common compounds in wine and as natural products from other sources. Previous methods of synthesis have followed a variety of different routes although many experimental details are unclear and of limited value. It was therefore felt that a gap exists in the literature with regard to an effective synthesis for these compounds and the development of a new synthetic pathway to afford both compounds, and analogues thereof, from a common starting material would be of value. The aim of this project was therefore to combine these areas and utilise 1,2-dioxine chemistry for the synthesis of the furanoid and anhydrofuran linalool oxides, with a key step in the synthesis being the ozonolysis of a bicyclic bridged 1,2-dioxine to yield the necessary keto-aldehyde precursor. Since little attention has been focussed on exploring the ozonolysis reaction of bicyclic alkenes, particularly the alkene moiety of bicyclic 1,2-dioxines, the first part of this thesis is focussed on investigating the scope of this novel reaction. A range of 1,4-disubstituted bicyclic 1,2-dioxines and a steroidal 1,2-dioxine were used for this study, with their synthesis outlined in Chapter 2. Chapter 3 presents the results for this section of work, where it was found that upon reaction with ozone, the nature of substrates at the bridgehead positions of the 1,2-dioxines had a major influence on the outcome of the reaction; with some of the substrates giving the expected dialdehydes, whilst others behaved in an unexpected manner towards ozone. Additional experiments were then conducted to provide further insight into these unusual results. The potential mechanism involved in these rearrangements is also discussed, with several plausible options presented. Chapter 4 presents some Ab-Initio computational analyses to support the preliminary mechanistic insights into the ozonolysis reaction, with specific regard to bicyclic 1,2-dioxine systems. This was done by examining the relative energy differences for all possible isomers involved in each stage of the proposed mechanism in order to locate the lowest energy pathway, and therefore that which is most likely followed. The second part of this thesis, presented in Chapter 5, was to utilise this novel transformation as a key step in the synthesis of both the furanoid and anhydrofuran linalool oxides, from a common starting material. The pathway began with the synthesis of a new bicyclic 1,2-dioxine, followed by successful ozonolysis and ring-contraction into the core 2,2,5-trisubstituted THF. It was found that having a hydroxyl α to either the furan or dioxine ring systems could be problematic and led to unwanted ring-opening and further rearrangements. Investigations revealed that this could be overcome upon protection of the hydroxyl, thereby enabling structural manipulation of the other functional groups to proceed smoothly. Research along the synthetic pathway did reveal a new potential route to dioxabicyclo[3.2.1]octanes, with two new bicyclic compounds formed as a result of selective 1,6-cyclisation of a cis-γ-hydroxydione intermediate, a reaction previously unseen within the literature. Time was a limiting factor in being able to complete the total synthesis of the desired compounds, but the major ground work was achieved. The C₂ functionalisation of the THF ring was successfully completed, and some new and novel chemistry was uncovered, which has further enhanced the understanding of the chemical nature of these types of compounds, along with their potential use in the synthesis of these important wine aroma compounds and other natural products.
Advisor: Taylor, Dennis Kenwyn
Elsey, Gordon Michael
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Agriculture, Food and Wine, 2011
Keywords: 1,2-dioxines; ozone; ozonolysis; furanoid oxides; wine compounds; total synthesis; ozonolysis mechanism
Appears in Collections:Research Theses

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