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Lewis acid-promoted synthesis of pyrazole building blocks.

Comas-Barceló, Júlia (2016) Lewis acid-promoted synthesis of pyrazole building blocks. PhD thesis, University of Sheffield.

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Abstract

The present work investigated copper(II)-promoted regioselective synthesis of disubstituted pyrazole scaffolds via cycloaddition reactions between sydnones and alkynes. Cu(OTf)2 has been found to mediate the formation of 1,3-pyrazoles, while Cu(OAc)2·H2O promotes the exclusive formation of the 1,4-regioisomer. Both transformations have been optimised and the scope has been explored for both reactions. A mechanistic proposal is also reported herein that has been derived from both experimental and theoretical investigations, the latter performed in collaboration with colleagues at Universidad del País Vasco (Spain). Furthermore, a catalytic variant of the synthesis of 1,4-disubstituted pyrazoles has been developed using Cu(OAc)2 supported in modified silica gel and, in collaboration with Future Chemistry Holding BV and Radboud University (the Netherlands), this methodology has been implemented under continuous flow. A directed cycloaddition of sydnones and alkynylboranes has also been developed. A range of substrates have been synthesised and subjected to cycloaddition conditions, showing that only pyridine- and quinoline-derived substrates afforded the desired pyrazole products. Mechanistic studies using NMR spectroscopy have also been carried out. Finally, the diastereoselective addition of Grignard reagents to a sydnone sulfinimine derivative has been studied, using this strategy to generate bicyclic pyrazole scaffolds containing stereogenic centres after a functionalisation-cycloaddition tandem process.

Item Type: Thesis (PhD)
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > Chemistry (Sheffield)
Depositing User: Dr Júlia Comas-Barceló
Date Deposited: 24 Jan 2017 09:33
Last Modified: 24 Jan 2017 09:33
URI: http://etheses.whiterose.ac.uk/id/eprint/15943

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