Investigations into the Manipulation of 1,2,3-Triazoles and Towards an Asymmetric ‘Click’ Reaction of Meso Bis-Alkynes
This thesis describes the synthetic approaches undertaken to generate various substituted 1,2,3-triazoles and a small group of bis alkyne-containing compounds, followed by their attempted application in an asymmetric ‘click’ reaction. The first chapter gives an outline to the importance of desymmetrization within organic synthesis, providing examples of the types of stereoselective reactions found within the literature. Attention is then focused on the field of ‘click’ chemistry, specifically the copper-catalysed azide-alkyne cycloaddition (CuAAC), its mechanistic studies and recent applications. Chapter two contains the results and discussion of the project and begins with the application of the CuAAC reaction to produce a simple 1,4-disubstituted 1,2,3-triazole from its two coupling partners, an azide and an alkyne, in near quantitative yields. The 1,4-disubstituted triazole is then transformed to its corresponding triazolium salt, with the longer alkyl chains only giving 40-45% product. They are then reacted with potassium tert-butoxide to generate the 1,5-disubstituted 1,2,3-triazole in yields of 83% or above. The reaction steps were optimised to give a standard procedure for the conversion of 1,4- to 1,5-triazoles, with a small series of test reactions giving overall yields of up to 90%. The second section of the results and discussion chapter centres on the development of meso bis-alkynes which were to be used in the evaluation of an asymmetric ‘click’ reaction. A number of synthetic approaches to these compounds are described, with most falling short of their final target compound, and either needing further work or a redesign of the target compound itself. One target compound, meso-1,2-bis-(prop2-yn-1-ol)benzene 29, was synthesised and a series of further meso bis-alkynes produced by various additions to the propargylic alcohol. Evaluation of the asymmetric ‘click’ reaction using this group of compounds under a wide selection of reaction conditions gave no successful results, all returning only starting material. Chapter two concludes with a brief summary of future work. Finally, chapter 3 contains full experimental details for the synthetic studies carried out in the preceding chapters.
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