| Summary: | <p>The homolytic Brook rearrangement is discussed and homolytic fragmentations of epoxides and epoxysilane chemistry are reviewed.</p> <p>Thiyl radical induced isomerisation was performed on spiro alkenylepoxysilanes to generate novel alkenyl-α-trimethylsilylaldehydes rather than the products of radical Brook rearrangement. The trimethylsilylaldehydes were shown to isomerise on heating to silyldienol ethers and, <em>via</em> the addition of a Grignard reagent, to act as stereoselective vinyl cation equivalents. Attempts to extend the scope of the isomerisation to non-rigid systems met with failure.</p> <p>A review of the antibiotic Roseophilin is presented. Cycloaddition-fragmentation approaches to medium and large rings are reviewed as a prelude to our first route, the proposed Michael addition-retro-aldol fragmentation of the Diels-Alder adduct derived from isopropyl-cyclopentadiene and cyclodec- 2-yn-1-one. The novel ynone, synthesised <em>via</em> the intramolecular Friedel-Crafts acylation of 10-trimethylsilyl-9-decynoyl chloride, was found to isomerise readily to bicyclo[4.4.0]dec-1(6)-en-2-one therefore the model Diels-Alder reaction with cyclopentadiene was effected in one-pot from the cyclisation precursor. Details of the attempted fragmentation of tricyclo[10.2.1.0<sup>2,11</sup>]pentadeca-2(11),13-dien-3-one are then described but, due to inconclusive results, an alternative study was instigated.</p> <p>The use of free-radical macrocyclisations in the synthesis of large rings is reviewed with particular reference to the synthesis of natural products. Three strategies for the formation of a bicyclo[10.2.1]pentadecanone skeleton are reported, and subsequent model studies described. Cuprate additions to vinyl lactones and epoxides are discussed. The preferred strategy, involving a cycloalkyl tether between the radical donor and radical acceptor groups, was extended to a system which was derived from the addition of various cuprates to 2-oxabicyclo[3.3.0]oct-7-en-3-one The preparation of cuprates derived directly from 6-iodohexan-1-ol and 1-chloro-6-iodohexane is described. The trans- cuprate addition products were converted successfully to bicyclo[10.2.1]pentadec-12-en-3-one, and the <em>cis</em>- analogues, accessible through a novel regio- and stereoselective hydroboration-fragmentation reaction of 7- (6'-chlorohexyl)-2-oxabicyclo[3.3.0]oct-7-en-3-one, led to bicyclo[10.2.1]pentadec- 13-en-3-one. The successful cyclisations of model oximes, to form nitrones having the correct connectivity for the third ring of Roseophilin, are described.</p> <p>Cuprate additions to 6-(1'-methylethyl)-2-oxabicyclo[3.3.0]oct-7-en-3-one resulted in <em>anti</em>- attack; the <em>cis</em>- adducts were inaccessible <em>via</em> the above methodology but a few intermediates in the <em>trans</em>- series were prepared. Future routes and modifications to the methods developed are then discussed.</p>
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