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dc.contributor.advisorSmith, Andrew David
dc.contributor.authorCampbell, Craig D.
dc.description.abstractThis work describes the application of a variety of Lewis bases, encompassing predominantly N-heterocyclic carbenes (NHCs), but also the use of imidazoles, aminopyridines, amidines and isothioureas, as effective catalysts in the dearomatisation of heterocyclic carbonates, predominantly the rearrangement of oxazolyl carbonates to their C-carboxyazlactone isomers by means of the Steglich rearrangement. This rearrangement reaction has been investigated extensively, with the development of simplified reaction procedures and the invention of domino cascade protocols incorporating this transformation. In an attempt to understand the mechanism of this O- to C-carboxylation process, a number of interesting observations have been made. Firstly, the class of NHC has an important factor in promoting the rearrangement, with triazolinylidenes being the most effective. Secondly, an interesting chemoselectivity has been delineated using triazolium-derived NHCs, prepared using weak bases (typically Et₃N) or strong metallated bases; both alkyl and aryl oxazolyl carbonates undergo smooth rearrangement with triazolinylidenes derived from strong metallated bases such as KHMDS, while only aryl oxazolyl carbonates undergo rearrangement using Et₃N. Extensive effort has focused towards the development of asymmetric variants of these protocols, primarily towards the design, synthesis and evaluation of chiral NHC precatalysts. To this end, a number of chiral azolium salts have been prepared, encompassing a number of different NHC classes, including C₁- and C₂-imidazolinium salts, C₂-imidazolium salts and a range of triazolium salts. Efforts towards the asymmetric catalysis of the Steglich rearrangement of oxazolyl carbonate substrates have given an optimal 66% ee. Similar rearrangements have been demonstrated with the related furanyl heterocyclic substrate class, producing a mixture of α- and γ-carboxybutenolides. In contrast to the analogous oxazolyl carbonates, the regioselectivity of this rearrangement is dependent upon the nature of the Lewis base employed. Amidines and aminopyridines give a mixture of the α- and γ- regioisomers with generally the α-regioisomer being preferred, while a triazolium-derived NHC gives rise to predominantly the thermodynamically more stable γ-carboxybutenolide. Using amidines or aminopyridines, this rearrangement has been shown to proceed via an irreversible C-C bond-forming process, but in contrast, the rearrangement using the NHC proceeds via an equilibrium process with an optimised regioselectivity of >98:2 for the γ-carboxybutenolide regioisomer over the α-regioisomer. Whilst the asymmetric variant using chiral NHCs has proven unfruitful, rearrangements using a chiral isothiourea have given high levels of regioselectivity towards the α- regioisomer and with excellent levels of enantiodiscrimination (77–95% ee).en_US
dc.publisherUniversity of St Andrews
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
dc.subjectLewis baseen_US
dc.subjectN-heterocyclic carbene (NHC)en_US
dc.subjectSteglich rearrangementen_US
dc.subjectCarboxyl transferen_US
dc.subjectQuarternary amino aciden_US
dc.subject.lcshOrganic compounds--Synthesisen_US
dc.subject.lcshCarbenes (Methylene compounds)en_US
dc.subject.lcshHeterocyclic compoundsen_US
dc.subject.lcshAromatic compoundsen_US
dc.subject.lcshBases (Chemistry)en_US
dc.subject.lcshRearrangements (Chemistry)en_US
dc.titleLewis base-promoted organocatalysis : O- to C-carboxyl transfer reactionsen_US
dc.contributor.sponsorCarnegie Trust for the Universities of Scotlanden_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US

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