Abstract
Studies towards C–N bond activation and cleavage, involving aryl, benzyl, aziridine, and pyrrolidine systems are presented. The work aims to develop a novel method, or methods, for the cleavage of C–N bonds without the requirement of directing groups or quaternisation strategies.Examination of secondary phosphine oxide ligands as amphoteric, transient directing groups for the cross-coupling of aryl amines has been carried out, resulting in a successful proof-of-concept reaction. Extensive optimisation studies have been undertaken, resulting in no advancement in yield, and so exploration in this area has not been advanced further at this time.
A new method for the efficient conversion of α-primary benzylamines into benzyl iodides has been developed. Advancement of this discovery has resulted in novel methods for the telescoped twostep cross-coupling of benzylamines, and the nucleophilic substitution of benzylamines, via benzyl iodide intermediates. This method does not require directing groups, and isolation of the benzyl iodide intermediate is not necessary for effective transformations.
The scope of the benzylamine cross-coupling has been expanded to include α-secondary benzylamines, with unique cross-coupling conditions developed for this procedure. This transformation is rendered challenging by competing iodide elimination reactions during the synthesis of α-secondary benzyl iodides, and competing β-hydride elimination during cross-coupling.
Additionally, the established protocol for the conversion of amines into halides has been applied to the ring opening of aziridines and pyrrolidines. An unusual mechanism was observed upon the application of the developed conditions to an aziridine substrate, though ring opening was effective. Furthermore, efficient ring opening was achieved upon application of the developed conditions to a 2-aryl pyrrolidine substrate, though competing alkene formation was also observed. Optimisation studies revealed an efficient method for the ring opening of 2-aryl pyrrolidines to give ester or bromide intermediates.
Date of Award | 6 Dec 2022 |
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Original language | English |
Awarding Institution |
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Supervisor | Paul G Pringle (Supervisor) & John Bower (Supervisor) |
Keywords
- Cross Coupling
- C-N bond cleavage
- Nucleophilic substitution
- Ring Opening