Bismuth-Mediated Arylation of Weak Nucleophiles

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Ruffell, Katie (2023) Bismuth-Mediated Arylation of Weak Nucleophiles. PhD thesis, University of Nottingham.

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Abstract

Building upon recent advances in bismuth-mediated arylations which have seen the development of mild transmetallation procedures and utilisation of bismacycle scaffolds, several methodologies for the bismuth-mediated arylation of weak nucleophiles have been established.

The development and scope of a procedure for the bismuth-mediated ⍺-arylation of cyclic 1,3-diones with sterically demanding boronic acids is described in Chapter 2. The one-pot process utilises a bismacycle precursor and, through a two-step process involving transmetallation and oxidative arylation, provides direct access to ⍺-arylated cyclic 1,3-diones. Identification and interrogation of reactive Bi(V) intermediates was instrumental to the optimisation process, with Bi(V) intermediates found to influence both the steric tolerance and the selectivity of the reaction. The mild nature of the developed system is demonstrated through a broad substrate scope and, in combination with a robustness screen, highlights the compatibility of the procedure with a diverse array of functionality including halides, alkenes, carboxylic acids, esters and aldehydes. Extension of the protocol towards the arylation of fluoroalkyl 1,3-diones is presented in Section 2.5. The system incorporates the oxidative arylation step within a one-pot procedure, which efficiently converts the ⍺-arylated diones into fluoroalkyl pyrazoles via condensation with hydrazine reagents.

Chapter 3 builds on the success of the bismacycle methodology, with the development and scope of a protocol for the bismuth-mediated O-arylation of 2- and 4-pyridones described. The procedure demonstrates complete O-selectivity, providing access to phenoxypyridines with a range of sterically demanding and synthetically useful functionality tolerated in the mild two step, transmetallation and oxidative arylation process. A series of substituted bismacycles were synthesised and assessed in the arylation reaction, allowing the effect of modifying the electronic and steric properties of the bismacycle to be studied. The origin of the O-selectivity observed in the procedure, which stands in contrast to previous reports, was investigated experimentally and computationally. DFT calculations highlight the influential role of the geometry and hydrogen bonding interactions of the bismacycle scaffold in the regioselectivity of the reaction.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Ball, Liam
Keywords: arylation, Bismuth, organobismuth compounds, organic synthesis
Subjects: Q Science > QD Chemistry > QD241 Organic chemistry
Faculties/Schools: UK Campuses > Faculty of Science > School of Chemistry
Item ID: 72284
Depositing User: Ruffell, Katie
Date Deposited: 31 Jul 2023 04:40
Last Modified: 31 Jul 2023 04:40
URI: https://eprints.nottingham.ac.uk/id/eprint/72284

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