Approaches to the Total Synthesis of the Complanadines

In this thesis is presented work carried out during the course of the last 42 months. It concerns approaches towards total syntheses of the complanadine alkaloids. The main focus is the development of a model system to establish the viability of the key step in our proposed route to the complanadines. The thesis is divided into five chapters. Chapter 1 is an introduction to the complanadines, their biological activity and accomplished total syntheses to date. A brief introduction to the Diels–Alder reaction and selected examples of its application in the total syntheses of natural products are given. The Kondrat’eva oxazole–olefin hetero-Diels–Alder reaction as a method of pyridine formation is described and its application in the total synthesis of natural products is reviewed. Chapter 2 is the first part of the results and discussion section. It details our retrosynthetic analysis of complanadine A, outlines the corresponding proposed forward synthesis and presents a model system designed and synthesised to test the applicability of the Kondrat’eva oxazole–olefin hetero-Diels–Alder reaction in the context of our proposed total synthesis. Chapter 3 discusses work carried out in approaches to the total synthesis of complanadines and their monomeric subunit, lycodine, by means of the methodology developed in the previous chapter. Chapter 4 is the experimental section, which gives descriptions of the synthetic procedures employed and spectroscopic data for all compounds synthesised, both novel and previously reported, as discussed in Chapter 2 and Chapter 3. Supplementary information such as X-Ray data for synthesised compounds and selected NMR spectra are enclosed in the appendices.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Concise Synthesis of 1,4a-Bifunctionalised Decalin Building Blocks by C-H Activation of Decalin

Friedel-Crafts acylation of decalin introduces functionality at C1 and C4a, which may be elaborated to novel building blocks possessing a methyl ketone, methyl carbinol, or vinyl group at the ring junction

Concise synthesis of 1,4a-bifunctionalised decalin building blocks by C-H activation of decalin

Friedel-Crafts acylation of decalin introduces functionality at C1 and C4a, which may be elaborated to novel building blocks possessing a methyl ketone, methyl carbinol, or vinyl group at the ring junction

A Model System for the Synthesis of Complanadine Alkaloids by “Diverted Kondrat’eva” Oxazole–Olefin Cycloaddition

A synthetic approach to complanadine alkaloids is described which employs a Kondrat’eva reaction to construct the pyridine rings. The viability of this approach is demonstrated by its application to a model substrate accessed from unfunctionalized decalin. The key transformation affords the desired tetracyclic architecture with unprecedented incorporation of substituents on the pyridine ring, implicating the oxazole α-hydroxy group as an active participant in the cycloadduct fragmentation process

A Model System for the Synthesis of Complanadine Alkaloids by “Diverted Kondrat’eva” Oxazole–Olefin Cycloaddition

A synthetic approach to complanadine alkaloids is described which employs a Kondrat’eva reaction to construct the pyridine rings. The viability of this approach is demonstrated by its application to a model substrate accessed from unfunctionalized decalin. The key transformation affords the desired tetracyclic architecture with unprecedented incorporation of substituents on the pyridine ring, implicating the oxazole α-hydroxy group as an active participant in the cycloadduct fragmentation process

C–H Functionalization of sp³ Centers with Aluminum: A Computational and Mechanistic Study of the Baddeley Reaction of Decalin

Decalin undergoes reaction with aluminum trichloride and acetyl chloride to form a tricyclic enol ether in good yield, as first reported by Baddeley. This eye-catching transformation, which may be considered to be an aliphatic Friedel–Crafts reaction, has not previously been studied mechanistically. Here we report experimental and computational studies to elucidate the mechanism of this reaction. We give supporting evidence for the proposition that, in the absence of unsaturation, an acylium ion acts as a hydride acceptor, forming a tertiary carbocation. Loss of a proton introduces an alkene, which reacts with a further acylium ion. A concerted 1,2-hydride shift/oxonium formation, followed by elimination, leads to formation of the observed product