Kenny, Miles and Franckevicius, Vilius (2017) The selective palladium-catalysed decarboxylative coupling of nucleophiles in the presence of propargylic electrophiles. PhD thesis, Lancaster University.
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Abstract
This thesis describes the development of a palladium-catalysed chemo- and regioselective decarboxylative coupling of 1,3-dicarbonyl compounds and nitrogen nucleophiles in the presence of propargylic electrophiles. The first part of this thesis focuses on the palladium-catalysed cross-coupling reaction involving two 1,3-dicarbonyl compounds in a regio- and chemoselective manner via an allylic linker. The reaction is applied to a wide range of substrates and forms two C–C bonds and installs two all-carbon quaternary centres. Mechanistic studies to help deduce the mechanism of the reaction are described, which shows that by utilising a propargyl enol carbonate as one of the coupling partners, the regioselectivity of this process can be predictably controlled. The second part of this thesis focuses on the palladium-catalysed crosscoupling reaction of 1,3-dicarbonyl compounds with indole, pyrrole, imidazole and pyrazole nucleophiles via an allylic linker. Despite the weakly acidic nature of N-heterocycles, the reaction proceeds with good efficiency, complete regio- and chemoselectivity and broad substrate scope. Mechanistic studies have also been carried out to help deduce the mechanism of the reaction. The third part of this thesis centres around the development of the palladiumcatalysed cross-coupling reaction of two 1,3-dicarbonyl compounds in an enantioselective manner. Focus is given to the enantioselective alkenylation and enantioselective allylic alkylation reactions. Optimisation of the reaction conditions as well as the expansion of the substrate scope is described. Finally, a discussion of future work, comprehensive conclusions as well as experimental procedures for the preparation of new compounds, backed up by full analytical characterisation, are disclosed.