Synthesis of multi-heteroaromatic compounds by platinum-catalysed nucleophilic addition to allenes

Cooper, Lisa (2017) Synthesis of multi-heteroaromatic compounds by platinum-catalysed nucleophilic addition to allenes. Doctoral thesis, University of East Anglia.

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This thesis describes the extensive investigation into the platinum-catalysed double addition of nucleophiles to allenes and in particular, our efforts towards the synthesis of 2,3’-bis-indolyl methanes (BIMs), which are important compounds with potential biologically important properties. The first chapter will describe the background of both inter- and intramolecular addition reactions to allenes with a range of different nucleophiles and array of metal catalysts. The latter part of this chapter will focus on the two synthetic strategies for BIM formation, firstly, the classical approach involving the Friedel-Crafts reaction between indoles and carbonyl compounds using protic or Lewis acid catalysis and secondly, the more recent methods involving the use of transition metal catalysis for the addition of indoles to π-bonds such as alkynes, allenes and cyclopropene via direct double hydroarylation.
The first part of the results and discussion chapter describes the attempts to expand the scope of the inter-intermolecular addition reaction of heteroatom and heteroaromatic nucleophiles to a model allene, generating a range of bis-substituted products. Despite an extensive investigation of both nucleophiles (e.g. imidazole, pyrazole, thiophenol and aniline) and the reaction conditions (e.g. incorporation of silver salts for chloride abstraction and gold catalysis), we could not extend the method efficiently enough for the formation of these compounds. Therefore, the second part of this chapter focuses on the successful intra-intermolecular platinum-catalysed addition reaction of an external indole to an indolyl allene with subsequent formation of 6-endo cycles, 2,3’-BIMs or tris- and allylic derivatives.
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This section describes the optimisation of the reaction conditions to favour the formation of the desired 2,3’-BIM, an investigation to determine the effect that substituents on either the indolyl allene or the external indole has on the overall formation of the 2,3’-BIM and the 6-endo cycles, and a detailed mechanistic investigation to determine the overall mechanism of the reaction. A trend was found with EDG favouring the formation of the desired 2,3’-BIM and the EWG favouring the formation of the 6-endo cycles or the tris- and allylic derivatives. The mechanistic investigation revealed that the 6-endo cycles are intermediates in the formation of the 2,3’-BIM, with a platinum carbene complex as the key intermediate between the three products.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Chemistry
Depositing User: Jackie Webb
Date Deposited: 30 Apr 2018 11:34
Last Modified: 31 Jul 2019 00:38


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