A series of acrylate esters and selected analogues have been reacted with pyridine-2-,pyridine-3-, and pyridine-4-carboxaldehydes in the presence of diazabicyclo[2,2,2]octane (DARCO) to afford a range of Baylis-Hillman products. The pyridine-2-carboxaldehyde-derived products have been acetylated using acetic anhydride and the kinetics of the thermal cyclisation of the acetylated compounds to indolizines was investigated using proton NMR spectroscopy. The first-order kinetics of the cyclisation has been confirmed and the influence of substituents on the first-order rate constant, kₒbs has been examined. The kinetic data has been shown to be consistent with the previously proposed mechanism in which loss of the acetate group is ratedetermining. Each of the cyclisations was also monitored at three different temperatures permitting evaluation of the activation parameters. The Baylis-Hillman products and related acetylated derivatives were treated at room temperature with sodium methylthiolate; the hydroxy precursors were observed to undergo conjugate addition with a degree of diastereocontrol but the acetylated derivatives favoured an apparent SN¹ displacement of the acetate group.

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A series of <i>N</i>-acylated and –alkyated aminobromopyridines were prepared, and under 2,2’-azobisisobutyronitrile (AIBN) initiation in the presence of <i>n</i>-tributyltin hydride (Bu₃SnH), readily underwent cyclisation to produce 4-aza and 7-azaoxindole derivatives. Upon recrystallisation in polar solvents in the presence of atmospheric oxygen, these compounds were found to undergo quantitative autoxidation.  Inspection of NMR and MS data suggest that the mechanism proceeds by hydrogen abstraction to form a hydroperoxide intermediate. The second part of the study reveals a simple and effective synthesis towards pyrrolo[2,3-<i>d</i>]pyrimidine derivatives as substitutes for purine analogues.  The purine-type nucleus is secured <i>via </i>tributyltin hydride mediated radical cyclisation, which provides a convenient route to access compounds for studies of biological activity and structure activity relationships. The third part describes radical addition of iodopyridines and functionalised pyrimidines to arenes, effected under mild conditions using tris(trimethylsilyl)silane and oxygen to promote the bimolecular radical addition pathway.  Initial reactions yielded intractable pyridine products with tris(trimethylsilyl)silane by-products. This was overcome by initial quaternisation of the heterocycles. The fourth part of the study  concerns the synthesis of the pyrimidine backbone unit of the natural product isolated from the <i>heterostemma brownii.  </i>This was obtained by the regioselective radical addition of halopyrimidine to electron-deficient methyl methacrylate (MMA). The final part describes the radical translocation reaction and the effect of variation in cycloalkane ring sizes and electron-donating ability.  This provided a route towards horsfiline derivatives. Under the high temperatures experienced by the horsfiline precursors this serendipitously yielded macrocyclic pyrimidines.

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This thesis describes investigations into tandem catalysed synthesis of polycyclic heteroatom containing molecules and the utilisation of high throughput screening (HTS) methodologies to identify active catalysts. Methodology for the high throughput screening of in situ generated metal complexes as catalysts was developed. UV spectroscopy and Capillary Electrophoresis (CE) were developed as effective methods of screening combinatorial arrays of complexes as catalysts. HTS methodologies were applied to the screening of in situ generated complexes as catalysts for the hydroamination of 2-(2-phenylethynyl)aniline. Two complexes were identified to be highly active hydroamination catalysts in acetone; the in situ combinations of [Rh(CO)2Cl]2/mesBIAN 38/NaBF4 and Ir(COD)Cl]2/NaBF4. Also identified in this work was the formation of the unusual N-(2-methylvinyl)-2-phenylindole catalysed by [IrCp*Cl2]2/NaBF4 from 2-(2-phenylethynyl)aniline via the incorporation of one molecule of acetone. Complexes of the type [Cp*MCl(N-N)][X] were synthesised (M = Rh(III) / Ir(III)), N-N= bpm 31, bim 32, dmbpm 61, bik 62, mesBIAN 38 and mesim-mim 63, X= Cl-, BF4-, [Cp*MCl3]-). Where N-N was bpm 31 or bim 32 and there was no alternate counterion present, bimetallic complexes formed containing the counterion X= [Cp*MCl3]-. The three dimensional, solid state, structures of the cationic fragments of the bimetallic complexes [Cp*MCl(N-N)][X] (M= Ir, X= [Cp*IrCl3]-, N-N= bpm 31 and bim 32; M= Rh, X= [Cp*RhCl3]-, N-N= bpm 31; M= Ir, X= BF4 -, N-N= bim 32, mesBIAN 38 and mesim-mim 63) are presented. Abstraction of the chloride, in complexes of the type [Cp*IrCl(N -N)]BF4, by AgBF4 created active catalysts in situ with the best catalyst in the series for the hydroamination of 2-(2-phenylethynyl)aniline [Cp*IrCl(mesBIAN)]BF4/AgBF4. Investigations performed into the synthesis of N-(2-methylvinyl)-2-phenylindole catalysed by [IrCp*Cl2]2/BF4- have shown that the most likely potential mechanism proceeds via the initial catalysed formation of the imine followed by metal promoted cyclisation. The isolation of the complex [IrCl2(2-(2-phenylethynyl)aniline)Cp*] and investigation into its reactivity showed it to be a potential reactive intermediate in the catalytic cycle. Investigation into catalysed C-C bond formation of N-propargylindole identified the in situ generated complex [Rh(CO)2Cl]2/PPh3 as a catalyst for the generation of pyrroloquinoline as a 1:1 mixture of regioisomers.

Thesis (M. Phil.)--University of Hong Kong, 1989.

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