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Palladium-catalysed desulfinative cross-coupling reactions: Leveraging mechanistic insights for reaction optimisation

Abstract:

In this thesis, the mechanism of the palladium-catalysed desulfinative cross-coupling of aryl bromides and (hetero)aryl sulfinate salts is investigated. The challenges that must be overcome to deliver improved, lower temperature versions of this process are discussed, and optimisation work based on these mechanistic insights is presented.

Chapter 1 is a literature review surveying the use of sulfinate salts in palladium-catalysed cross-coupling reactions. Particular emphasis is placed on the mechanism of these transformations and the structure of palladium sulfinate intermediates.

Chapter 2 describes the mechanistic studies of the palladium-catalysed desulfinative cross-coupling of 1-bromo-4-fluorobenzene and (hetero)aryl sulfinate salts. 2-Pyridyl and carbocyclic sulfinate substrates are compared, and different catalyst resting states and turnover limiting steps are established for the two classes of reagent. The role of the carbonate additive and the reduction of the palladium(II) precatalyst is also investigated.

Chapter 3 demonstrates the significance of the challenges associated with developing lower-temperature desulfinative cross-coupling reactions. A survey of a number of reaction parameters and their influence on the outcome of the reaction is presented.

Chapter 4 focuses on the use of the Xantphos ligand and the synthesis of Xantphos derivatives to promote desulfinative cross-coupling reactions at 100 °C.

Chapter 5 discusses the development of a desulfinamidative cross-coupling reaction using a primary aryl sulfinamide as the nucleophilic coupling partner. The feasibility of this process is demonstrated, and initial optimisation results are presented.

Chapter 6 discusses the conclusion of the research and the potential for future work.

Chapter 7 presents the experimental data.

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Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Oxford college:
St Hilda's College
Role:
Author
ORCID:
0000-0003-4777-345X

Contributors

Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Organic Chemistry
Oxford college:
Lincoln College
Role:
Supervisor
ORCID:
0000-0002-0636-6471


More from this funder
Funding agency for:
De Gombert, A
Grant:
1797010


DOI:
Type of award:
DPhil
Level of award:
Doctoral
Awarding institution:
University of Oxford


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