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The introduction to this thesis commences with a description of the mechanism of the Pauson-Khand reaction (PKR) as postulated by Magnus. Three examples of biologically active compounds synthesised using the stoichiometric PKR are presented, and the cobalt catalysed PKR is surveyed together with the asymmetric cobalt catalysed PKR. The first half of Chapter 2 describes research into the reaction pathway of a cobalt catalysed asymmetric PKR. Three enynes 68, 81 and 82 were synthesised together with the novel alkyne 80. Compounds 68, 80, 81 and 82 were used to synthesise the novel (BINAP)(enyne)C02(CO)4 complexes 89-92. X-Ray crystal structures were obtained for novel complexes 89 and 90. Variable temperature 31p NMR experiments were first carried out on complexes 89, 91 and 92 under nitrogen and all four complexes (89-92) were examined in the same way under an atmosphere of carbon monoxide. The variable temperature 31p NMR experiments under carbon monoxide with novel complexes 89, 91 and 92 resulted in the observation of a new resonance at 0 54 ppm. Observation of the resonance at 0 54 was found to be dependant on the presence ofan alkene moiety within the complexes. A (J bonded cobalt-alkyne complex (93) was identified by X-ray crystallography, which stimulated the synthesis of two enynes 94 and 95, containing internal alkyne moieties. Novel (BINAP)(enyne)C02(CO)4 complexes 98 and 99 were synthesised from enynes 94 and 95 and subjected to variable temperature 31p NMR experiments under carbon monoxide whereupon the new resonance at 054 was observed. The novel (BINAP)Co(CO)(CI) complex 100 was isolated and examined by X-ray crystallography, and the resonance at 0 54 was characterised by NMR spectroscopy and X-ray crystallography as the novel HCo(COh(BINAP) complex 101. The enynes (89, 91 and 92), water and the Pauson-Khand adduct 69 were investigated as a hydrogen source for the formation of complex 101 but the search was inconclusive. 31p NMR spectroscopy of the catalytic PKR revealed the presence of 101 in the PKR together with (BINAP)C02(CO)6 75. The second half of Chapter 2 describes the application of the catalytic PKR in the synthesis of drug candidates. Three reversible covalent inhibitors of cathepsin Sand K enzymes were designed. The development of a new intermolecular PKR utilising alkene reactants tert-butyl-2,5-dihydropyrrole carboxylate 124 and tert-butyl-2,3-dihydropyrrole carboxylate 125 was a~empte~.. An intramole~u~ar PKR was used to synthesise five potential inhibitor sequences, U8a-e, which exhibited poor selectlvity and low inhibition of the cathepsin Sand K enzymes.

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