Thesis
A study of the electrophilic and radicophilic activation of certain classes of amines
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2024
- Thesis identifier
- T17019
- Person Identifier (Local)
- 201990149
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Chapter 1: A novel method for the preparation of cyclic α-aminomethylammonium salts was developed. These were allowed to react with various nucleophiles (Scheme I) [illustration in text] in order to probe the reactivity of the αaminoalkylammonium salts (e.g. II – IV) such as those proposed as intermediates (I) in the work of Barham and co-workers.1 Scheme I – Treatment of cyclic α-aminomethylammonium salts with nucleophiles under: (i) acidic conditions (left); and (ii) basic conditions (right). The nucleophiles tested included various anionic species including phenolates, enolates, thiolates, lithium acetylides, and deprotonated nitriles as well as N-heteroarenes such as pyrroles, indoles and azoles, thereby expanding the list of nucleophiles which are known to react with αaminomethylammonium salts. Neutral nucleophiles (such as pyrroles, indoles and N,Ndimethylaniline) also reacted under acidic conditions to afford a variety of diamine products including a neuropeptide Y agonist, which formed in better yields than the literature reported Mannich reaction route. Chapter 2: Following on from previous work within the Murphy research group on the functionalisation of aryl alkyl ethers (VII) at the α-aryloxyalkyl position, a redox-neutral methodology (Scheme II) [illustration in text] for the αaryloxyalkylation of N-heteroarenes via their N-methoxyheteroarenium salts (such as VI) has been developed. During the course of this work, quinolines (such as XI) were also identified as privileged substrates for α-aryloxyalkylation without the need for prior N-functionalisation (as long as a stoichiometric oxidant is present, e.g. XII or K2S2O8) (Scheme III) [illustration in text] and attempts have been made to rationalise this finding. Scheme III – Conditions for the α-phenoxyalkylation of unactivated quinolines such as XI using aryl alkyl ethers. Furthermore, under these conditions dearyloxylation occurs as a side reaction, with evidence that this occurs via a radical scission or spin-centre shift mechanism involving homolysis or heterolysis of radical intermediates (such as XVI, Scheme IV) [illustration in text]. A methodology has also been developed which can promote dearyloxylation of α-aryloxyalkylquinolines (such as XIV) where desired. Chapter 3: Attempts were made to design an activated pyridinium salt bearing a sterically hindered N-substituent in order to promote para-selective α-aryloxyalkylation of pyridines. Elsewhere in our laboratory, it was found that using N-alkoxypyridinium salts with increasingly large alkyl groups was not an effective strategy. The use of N-silyloxypyridinium salts proved challenging due to difficulty in synthesising this type of compound. N-Benzyloxypyridinium salts and N-(Nmethyltosylamido)pyridinium salts afforded yields too low under the conditions required for αphenoxyalkylation to be synthetically useful. Using 2-(pyridine-1-ium-yl)succinate esters (such as XIX, Scheme V) afforded high para-selectivity when using PhOEt, but para-selectivity decreased significantly when using PhOMe. N-Arylpyridinium salts (Scheme V) [illustration in text] were then used as α-phenoxyalkylation substrates, with Nmesitylpyridinium salts (XXIV) giving exclusively para-functionalised products when reacted with PhOEt and a 10:1 ratio of para : ortho-substituted product when reacted with PhOMe. As with αaryloxalkylated quinolines, α-aryloxalkylated N-mesitylpyridinium salts were found to undergo Irphotocatalysed dearyloxylation (Scheme VI) [illustration in text].
- Advisor / supervisor
- Murphy, John A.
- Resource Type
- DOI
- Funder
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| Miniaturansicht | Titel | Hochladedatum | Sichtbarkeit | Aktionen |
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File | 2024-07-22 | Embargo |