HEERAN, DARREN (2018) Fluorinated Azaheterocycles. Doctoral thesis, Durham University.
|PDF - Accepted Version|
Fluorinated heterocyclic motifs have found wide application across the life science industries. Therefore, there is profound interest in the development of new and efficient methodology for the incorporation of fluorine into heterocyclic structures. This thesis is concerned with the development of processes for the incorporation of fluorine into the biologically important azaheterocycles, pyrroles and pyrido[1,2-a]pyrimidines, for which current methods are limited.
Firstly, the fluorination of pyrroles with SelectfluorTM was studied systematically. Pyrrole substrates bearing electron-withdrawing substituents were found to give fluorinated products but, in all cases, competing oxidation and subsequent polymerisation limited the attainable yields. From this, a tetrabromopyrrole was instead employed which, by lithiation and subsequent reaction with NFSI, gave access to polybrominated 2- and 3-fluoropyrroles. The bromine atoms could be used for subsequent derivatisation by debromolithiation and reaction with a range of electrophiles as well as palladium catalysed Suzuki cross-couplings to give access to a diverse library of highly functionalised fluoropyrrole products.
The synthesis of a fluorinated pyrido[1,2-a]pyrimidin-4-one scaffold was also investigated using a fluorinated building block approach. The cyclisation of 2-fluoromalonic acid with 2-aminopyridine in POCl3 gave a fluorinated pyrido[1,2-a]pyrimidin-4-one substrate which was further derivatised by Suzuki cross-coupling reactions.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Faculty and Department:||Faculty of Science > Chemistry, Department of|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||20 Apr 2018 12:33|