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Title: Lewis acid-promoted synthesis of pyrazole building blocks
Author: Comas-Barceló, Júlia
ISNI:       0000 0004 5993 2435
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2016
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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.
Supervisor: Harrity, Joseph P. A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available