No description available.

The tributyltin hydride/AIBN combination used to mediate radical cyclisations has become a common protocol in organic chemistry. This system which allows good substrate flexibility is a useful complement to ionic annulation reactions. However, the tin residues are highly toxic and difficult to separate from reaction mixtures. In this project, alternatives to tin have been used with varying success and a SPOS approach was adopted to minimise the problems associated with tin. Acyl radical addition to 2- and 3-substituted electron deficient pyrroles was used to construct a variety of interesting bicyclic compounds including pyrrolizine alkaloids nordanaidone and hydroxydanaidol. Acyl radical reduction was retarded by slow syringe-pump addition of tributyltin hydride in cyclohexane to the acyl selenide and AIBN in acetonitrile as a two-phase solvent system. Carbon monoxide saturation of the reaction vessel and solution was also necessary to inhibit decarbonylation in slow cyclisations.

No description available.

No description available.

The object of study of this thesis lies on the optimisation of the oxidative radical cyclisation methodology for the preferential formation of gamma-lactones from unsaturated alkyl malonate derivatives. <strong>Chapter 1</strong> introduces the concept of free-radical cyclisation; more extensive explanations are given for the intramolecular oxidative radical cyclisation using manganese(III) and copper(II) salts as oxidants. An overview of the contribution of the Burton group in the field is given, in which both the applicability and the limitations of the transformation are showcased. <strong>Chapter 2</strong> is concerned with the synthesis of the ethisolide family of natural products and one non-natural analogue, in which the oxidative radical cyclisation is key for the construction of the bis-gamme-lactone moiety present in such natural products. The initial limitations of the methodology allowed for the discovery of new conditions for the formation of chloro monocyclic systems and for the development of copper-free oxidative cyclisation conditions for gamma-lactone formation. <strong>Chapter 3</strong> reports the developments on the metal-free oxidative radical cyclisation. Bicyclic gamma-lactones were synthesised from all-carbon alkyl malonate derivatives through anodic oxidation via constant current electrolysis. The development of a novel ionic oxidative cyclisation is also discussed. <strong>Chapter 4</strong> describes our efforts towards the formation of both fused and spiro gamma-lactam-beta-lactone molecules, as potential analogues to proteasome inhibitors, from either gamma-lactam-gamma-lactones or exo-gamma-lactams precursors, previously synthesised through oxidative radical cyclisation. Full experimental details, NMR spectra for the natural products and for the non-natural analogue, and a comparison between the obtained and the previously reported NMR data are also provided.

This thesis is concerned with the development of cyclisation strategies that allow entry to polycyclic heterocycles and medium sized ring systems. Radical additions to pyridines are developed and methodologies explore the differences between the homolysis of C-Br and C-I bonds. Mechanisms are described for the unexpected ipso additions to the pyridines. Work towards the synthesis of the stegnans and dimethylgomisin illustrates the attempts to utilise the ipso addition to form medium sized ring systems. A new method of synthesising these medium sized ring systems is discussed. Progress towards a general methodology is described and shows the opportunities for which it could be utilised. A literature review of the synthesis of heterocycles via radical cyclisations is presented.

No description available.

Application of radical reactions in the organic synthesis for the formation of carbon-carbon bond has dramatically increased over the last fifteen years by virtue of their high degree of chemo-, regio- and stereoselectivity. The present thesis entitled "Radical Cyclisation based Approaches to 9-pupukeanone and Lignan Precursors" describes the application of radical reactions in the synthesis of isotwistane carbon framework present in pupukeananes, and b-arylmethylbutyrolactones, established precursors of various types of lignans. For convenience, the results are presented in two chapters, & ( I ) Radical annulation approach to chiral analogues of 9-pupukeanones; (2) Synthesis of (+-)-enterolactone and lignan precursors; and an appendix entitled 'Chiral synthons from (R)- carvone'. In each Chapter the compounds are sequentially numbered (bold and double underlined), and references are marked sequentially as superscripts and listed at the end of the Chapter. All the figures were obtained by direct xerox of the originaltNMR and muss spectra, and in some of them uninformative areas have been cut to save the space.

A new method for the synthesis of naphthalenes has been recently discovered. The Atom Transfer Radical Cyclisation (ATRC) of diverse 2-allylphenyl2',2',2'-trichloroacetates in the presence of a Cu complex afford schloronaphthalenes in good yields using either microwave or thermolytic methods of activation. A mechanism for the benzannulation reaction is proposed and experiments presented in order to validate this hypothesis. The use of 1,3-bis(2,6-diisopropylphenyl)imidazolium copper(I) chloride [(IPr)CuCl)] along with other metal carbenes is compared to the already reported CuCl/ligand system. Since the scope and synthetic utility of this new benzannulation reaction is restricted due to the use of the MW reactor, a solvent in which the thermal reaction can take place is reported, proving its efficiency in the synthesis of a range of substituted naphthalenes. The potential and versatility of the benzannulation reaction has been investigated. Studies towards the synthesis of gilvocarcin M which contains a tetracyclicaromatic core are presented. Gilvocarcins have potential use as anti-cancer agents and represent a member of the C-aryl glycosides found in natural products. Gilvocarcin M is a challenging target because there are a sparse number of total syntheses reported in the literature. The ATRC reaction of (vinyl)phenyl trichloroacetate has also been investigated, affording the synthesis of functionalised coumarins. The mechanism of this reaction has also been investigated, establishing that, in some cases, aretro-Kharasch reaction is observed.

In this project cyclisation chemistry using palladium and radical methodologies has been developed. The aim was to compare palladium and radical mediated cyclisations. Initially small molecules containing amine and amide functional groups were synthesised to screen the methodology. Later the design of these molecules was changed to be based on the imidoyl functional group. A series of N-benzyl protected aliphatic amine and amides were synthesised in the hope (with the aim of cyclisation) that they could be cyclised using both palladium and radical conditions. When these examples failed, which was attributed to the strain of the cyclic molecules, alternative precursors were sought. Initially, the N-protecting group was changed to a tosyl-group. However, when this had no positive effect, the size of the precursor molecules were examined. Two alternative amine precursors were designed which would remove the strain element in the cyclised molecules. The lengthy synthesis of these two molecules was not favourable for the development of methodology. Although it appeared that the cyclisations were now occurring it did not prove favourable to carry on down this path. The final part of this research project utilises imines and imidoyl selenides as radical and palladium cyclisation precursors respectively. A series of aromatic imines and imidoyl selenides were synthesised. The irnines were synthesised from amino-biphenyl and a range of p-substituted benza1dehydes. The corresponding imidoyl selenides were synthesised from amino-biphenyl and a range of p-substituted benzoyl chlorides to give the amides which in tum were converted to the target molecules via the imidoyl chlorides. The successful cyclisations using both methodologies resulted in a series of phenanthridines. This success of these cyclisations led to further precursors being developed which included bisphenanthridine, alkyne, alkyl and heteroaromatic precursors. However, most of the cyclisations of these molecules proved problematic and require further development of methodology.