Transition Metal Free Decarboxylative Halogenation and its Application in Cross-Coupling Chemistry

  • Jacob Quibell

Student thesis: Phd


The use of benzoic acids as aryl donors in cross-coupling reactions has recently become an exciting and growing field of chemistry. Partly due to the pioneering work of Gooßen who disclosed the seminal report on transition metal catalysed decarboxylative cross-coupling the area has enjoyed somewhat of a renaissance and now benzoic acids have been established as effective alternatives to traditional cross-coupling partners. Benzoic acids profit from being bench-stable, non-toxic and readily available, giving them an advantage over many other compounds used in cross-couplings. This thesis aims to give a thorough account of the development of a decarboxylative halogenation strategy and its application in cross-coupling chemistry (Scheme I). In order to provide an appropriate context to the novelty and utility of the methodology presented, it is first necessary to give a historical account of decarboxylative transformations. The first chapter will discuss the initial discoveries of synthetically useful decarboxylation procedures before exploring the recent expansion of the field of decarboxylative cross-coupling. The evolution of the decarboxylative halogenation reaction will also be detailed; starting from its origins as the Hunsdiecker reaction to the more modern methods disclosed recently. Chapter 2 will then give an account of the development of a transition metal free decarboxylative iodination reaction. The initial findings and optimisation of the reaction will be described before a thorough investigation into the scope is detailed. Preliminary mechanistic studies are also reported which hope to illuminate the differences between this procedure and other previously reported decarboxylative iodinations. The utility of the transformation will then be exhibited by using the resulting aryl iodide as a cross-coupling partner, coupling with either simple arenes or a second benzoic acid in a one-pot reaction. Expanding on these findings we will then look at the analogous decarboxylative bromination reaction (Chapter 3). Again, investigations into the scope and the mechanism of the reaction will be revealed. Finally we will look to show the applicability of both the decarboxylative iodination and bromination procedures towards arguably the most powerful of cross-coupling methods – the Suzuki-Miyaura reaction. Again occurring in a one-pot fashion we will show that this strategy can lead to the efficient synthesis of a wide range of (hetero)biaryls. In addition this method can also be used to effect a decarboxylative alkylation reaction, exhibiting a rare example of this transformation.
Date of Award31 Dec 2019
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorDavid Procter (Supervisor) & Igor Larrosa (Supervisor)

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