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Design and Synthesis of Chiral Triazolium and Thiazolium Salts Incorporating Hydrogen-Bonding Motifs as Organocatalysts



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Radoux, Emma Catherine 


The benzoin condensation is the rst reported example of organocatalysis, and has been studied and used in organic synthesis for over 200 years. Originally catalysed by the cyanide anion, the reaction can also proceed with thiamine as a catalyst. Since then, many N- heterocyclic carbene (NHC) catalysts have been developed for use in umpolung reactions between aldehydes and a range of coupling partners. However, stereoselectivity of the new chiral centre is dif cult to control: current existing methods employ steric hindrance of catalysts to in uence this, potentially at the cost of slower reaction times.To date, there are very few examples of NHC catalysts incorporating hydrogen-bonding motifs to exploit attractive forces in in uencing stereochemistry in these reactions. An overview of asymmetric organocatalysis and their different modes of action have been detailed. The structures of NHC catalysts and their mechanisms are discussed, and the reactions which are catalysed by these salts reviewed. Current shortcomings are addressed, and both the project and new catalyst designs are proposed. Synthetic routes to new triazolium and thiazolium salt catalysts with unreported chiral backbones are discussed. These involve 1,2-diamine derived salts, 1,4-diamine derived salts, amino acid-derived triazolium salts, and a bicyclic triazolium salt with a piperidine backbone. Representative catalysts from each of these categories were synthesised and the catalytic ability of the NHC salts in umpolung reactions investigated. All of the catalysts are demonstrated to be effective at obtaining yield and ee in the Stetter reaction. These catalysts are critically analysed, future work proposed.





Leeper, Finian


organocatalysis, carbene, benzoin, Stetter, enantioselective, thiazolium, triazolium, urea, thiourea, salt, NHC, N-heterocyclic carbene, chiral, stereoselectivity


Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge