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Interpretation of Additives Effects in Enamine Catalysis and Application in Mechanistic Studies

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Title: Interpretation of Additives Effects in Enamine Catalysis and Application in Mechanistic Studies
Authors: Hughes, Matthew James
Item Type: Thesis or dissertation
Abstract: Since 2000, a profusion of reaction types catalysed by functional organic molecules has steadily been discovered. Organocatalysis has thus become a major field of chemical research – but in spite of this, relatively few mechanistic studies have emerged. Additives can frequently alter reactivity in organocatalytic reactions, and can serve as powerful mechanistic probes. A holistic approach to understanding additives effects alongside other kinetic parameters has been shown to generate far deeper understanding of such processes. The research documented in this thesis strives towards the elucidation of the effects of additives in three important types of organocatalytic transformation. An extraordinary reversal of enantioselectivity upon the application of basic additives to the proline-catalysed amination reaction has been investigated. By varying the additive loading, and through screening a range of different additives – including a bespoke set of isosteric guanidine bases – it was revealed that a positive relationship exists between additive basicity and enantioselectivity. Investigations were extended to the application of a range of preformed prolinate catalysts that were found to exhibit even higher selectivity, dependent on the nature of the counter cation. When focus then turned to the intermolecular aldol reaction, remarkably different reactivity was again observed on the switch from proline catalysis to prolinate catalysis. Surprisingly, the altered active species was found to be a retroaldol catalyst, which gives rise to reversible aldol processes and increased catalytic activity. The mechanism of the Hajos–Parrish–Eder–Sauer–Wiechert reaction was examined with the aid of additives effects and deuterium labelling. Protocols were developed for studying the reaction under completely homogeneous conditions to allow deconvolution of solubility effects from intrinsic mechanistic effects. It was found that while acidic and basic additives can accelerate the reaction, this is entirely due to catalyst solubilisation. The implications of these findings have answered key questions of mechanistic debate.
Issue Date: 2013
Date Awarded: Mar-2013
URI: http://hdl.handle.net/10044/1/11064
DOI: https://doi.org/10.25560/11064
Supervisor: Armstrong, Alan
Department: Chemistry
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Chemistry PhD theses

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