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Shaken not stirred: unleashing the potential of mechanochemical synthesis

Nicholson, William 2021. Shaken not stirred: unleashing the potential of mechanochemical synthesis. PhD Thesis, Cardiff University.
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Abstract

Within this thesis is described a series of studies into performing organic synthesis under mechanochemical conditions during which new procedures were developed and advantages into using these methods discussed. Initial investigations focused on establishing a procedure for a mechanochemical Buchwald-Hartwig amination under ball milling conditions finding that the use of grinding auxiliaries was key for efficient mass transfer and high yields. Furthermore, the established procedure was applied to a range of aryl halide and amine substrates including the synthesis of an API. It was also investigated how the newly established conditions were found to be tolerant to air and moisture under ball milling conditions. During the substrate scope of the first investigation the direct amidation of simple esters was observed. This transformation was then investigated finding that the potassium tert-butoxide present in the Buchwald-Hartwig conditions was enabling this transformation. This method was then optimised and applied to a broad scope of esters and amines including the synthesis of five biologically active compounds. The developed conditions were then compared to solution and neat stirring conditions that had previously been established. Previously in the group the dimerization of benzylidene malonates had been discovered while investigating the formation of organomanganese halides mechanochemically. This reaction was studied in detail uncovering the possibility of ball milling enhancing the reactivity of manganese metal. Following, the generation of organomanganese halides directly from manganese metal and benzyl halides was investigated with promising initial results. This work was initially guided by some previous results obtained within the group that had uncovered some reactivity. Finally, included in an appendix, a reference to a manuscript discussing the investigations of the first examples of NHC catalysed reaction under ball milling conditions is presented. This discusses the application of ball milling to both the Benzoin and Stetter reactions catalysed by NHC’s and the application of asymmetric catalysts to these reactions for the induction of chiral information to the products.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Chemistry
Date of First Compliant Deposit: 10 February 2022
Last Modified: 10 Feb 2022 13:13
URI: https://orca.cardiff.ac.uk/id/eprint/147288

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