Robinson, Simon Jonathan; (1998) Catalytic and selective transition metal mediated isomerisations of allylic alkoxides to enolates. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The thesis is split into three chapters. The first chapter, the introduction, presents a broad review on enantioselective transfer hydrogenation reactions of organic compounds catalysed by transition metals, and their application in the asymmetric reduction of ketones, imines and activated carbon-carbon double bonds. Emphasis will be placed on mechanistic aspects, in addition to the effect of substrate and ligand architecture on the stereochemical outcome of the reaction. The second chapter will discuss a series of investigations into the application of transition metals in the catalysis of allylic alkoxides to metal enolates in a stereo, regio and enantioselective manner. This catalytic process represents a novel preparation of metal enolates which differs from the traditional approach utilising carbonyl compounds. The third and final chapter will involve a formal description of the experimental procedures that make up the results presented in chapter two. Several nickel based catalyst systems were investigated which had the potential for use as asymmetric catalysts, by simple replacement of the pre-existing ligands with chiral ligands. The Ni(COD)2/Ligand catalyst system demonstrated a greater activity than the NiCl2(Ligand) based catalyst system, and was therefore studied in greater depth. Excellent stereocontrolled enolate formation was demonstrated when using either benzene as solvent, or using pyridine as ligand, particularly when using a primary allylic alkoxide as substrate. These conditions, however, did not lead to significant improvements in stereoselectivity in tetrasubstituted enolate formation, although there was an exception with the alkoxide of (E)-2-methyl-1-phenyl-2-buten-1-ol, in which an (Z): (E) enolate ratio of 5 : 1 was obtained. It was also found that both the Ni(COD)2/Ligand and NiCl2(Ligand) catalyst systems demonstrated poor regiocontrol, where enolate regioisomers were possible. A range of prochiral allylic alkoxide substrates was tested using Ni(COD)2 in combination with a chiral ligand, but enantiomeric excesses in the isomerised products were not detected by chiral shift 1H-NMR, or by chiral GC. This lack of asymmetric induction is attributed to a number of possible factors, discussed here in detail. An investigation using deuterium isotopic labelling was also conducted in order to elucidate the possible mechanistic pathways in operation with the nickel catalyst. Rhodium as a catalyst was also investigated, and interesting results were obtained following an attempt to repeat a reported procedure in which an allylic alcohol was isomerised enantioselectively using a chiral rhodium catalyst. Modification of this catalyst by the addition of n-BuLi, afforded the first rhodium catalyst which was able to perform an isomerisation on the alkoxide of geraniol, in good yield. No enantiomeric excess in the product was detected, and discussions will be presented to account for this observation.

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