Abstract
The research in this thesis details the enantioselective α-functionalisation of aryl esters as C1-ammonium enolate precursors in isothiourea catalysis.Chapter 1 places the research presented in this thesis in the context of the previous literature. A range of enantioselective processes involving ammonium enolates and the recent emergence of aryloxide-promoted catalyst turnover in enantioselective Lewis base catalysis are highlighted. The aims of the research described in this thesis are also presented.
Chapter 2 describes the development of an isothiourea-catalysed enantioselective addition of 4-nitrophenyl (PNP) esters to tetrahydroisoquinoline-derived iminium ions. This work details preliminary studies and optimisation towards a sequential process involving an oxidation followed by isothiourea catalysis. A range of 15 substituted tetrahydroisoquinolines were accessed in ≈75:25 dr, up to 69% yield and up to 95:5 er. This represents the first report of an intermolecular process for the addition of C1-ammonium enolates to iminium ions.
Chapter 3 introduces the concept of photoredox catalysis and its use in the α- functionalisation of tetrahydroisoquinolines. The extension of the work described in Chapter 2 led to the development of a sequential photoredox/isothiourea-catalysed reaction. The highest yields and enantioselectivity were obtained using commerically- available tetramisole (5 mol%) and the use of iminium bromide ions generated in situ via photoredox catalysis using BrCCl₃ and Ru(bpy)₃Cl₂ (0.5 mol%). The scope and limitations of this procedure were investigated, with 36 different β-amino amide products obtained in ≈75:25 dr, up to 96% yield and up to > 99:1 er.
Chapter 4 details the development of an isothiourea-catalysed process for the enantioselective 1,6-conjugate addition of PNP esters to 2,6-disubstituted para-quinone methides. A range of products were obtained in ≈55:45 to 60:40 dr, up to 99% yield and up to 94:6 er. The diastereomeric products were separable in some cases by column chromatography.
Chapter 5 summarises the work described in this thesis and discusses potential future work within the area.
Date of Award | 26 Jun 2019 |
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Original language | English |
Awarding Institution |
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Supervisor | Andrew David Smith (Supervisor) |
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