VictorJuiz/thesis huggingface dataset:
Synthesis and trifluoromethylation of allylsilanes

The first part of this thesis presents a novel approach for synthesising enantioenriched cyclic allylsilanes via asymmetric ring-closing metathesis (ARCM). The second part of this thesis focuses on the reactivity of allylsilanes in electrophilic trifluoromethylation under transition metal and photoredox catalysis.
Chapter 1 provides a general introduction to existing methods for preparing compounds containing Si-stereogenic centres. The motivation for using ARCM to form Si-stereogenic centres is discussed. To set the stage for this work, the development of olefin metathesis as a tool in organic synthesis is briefly summarised.
Chapter 2 describes the synthesis of various prochiral silicon-containing trienes and their reactivity in Ru-, Mo- and W-catalysed ring-closing metathesis. . Following extensive screening of chiral catalysts, few catalysts were identified that enabled selective ARCM to access Si-stereogenic products in up to 98% ee. A systematic investigation of the relationship between the structure of the starting material (i.e., hydrocarbon chain length, steric and electronic properties of the silicon substituents) and the resulting efficacy in ARCM was undertaken, the results from these experiments are discussed. Importantly, this study represents the first example in which ARCM has been successfully used to desymmetrise prochiral substrates to form a new chiral Si centre (Scheme 1).
Chapter 3 provides a general introduction to the field of trifluoromethylation, with a special focus on recent applications of transition metal catalysts in Csp2–CF3 and Csp3–CF3 bond formation. A myriad of effective nucleophilic, electrophilic and radical trifluromethylating reagents have been developed during the past several years; the properties of these reagents and their compatibility with various modes of catalysis are summarised to provide a context for the second part of this thesis research.
Chapter 4 presents two novel methods for effecting trifluoromethylation of allylsilanes . First, it was discovered that the combination of an electrophilic trifluoromethlyating reagent and a copper catalyst effectively mediated trifluoromethylation of allylsilanes. The silicon substituent was crucial for improving the nucleophilicity of the substrate and dictating the regioselectivity of the Csp3–CF3 bond-forming step. With this method, alkyl or aryl substitution at the β-position of the allylsilane was critical for reactivity. Second, in a complementary study, it was found that copper could be replaced by a ruthenium photocatalyst and visible light. This latter method allowed for trifluoromethylation of substrates that were ineffective with copper catalysis. Mechanistic studies of both reaction systems were undertaken, and plausible reaction pathways for both reactions are proposed.
Chapter 5 gives full experimental procedures and characterisation data for all compounds.

Keywords: trifluoromethylation
metal catalysis
organosilanes
Advisor: Gouverneur, V
Homoclinic bifurcations

Previously obtained results from the study of homoclinic bifurcations in ordinary differential equations are presented. The standard technique of analysis involves the construction of a Poincaré map on a surface near to the homoclinic point. This map is the composition of an inside map, with behaviour linearized about the homoclinic point, together with an outside map, with behaviour linearized about the homoclinic orbit. The Poincaré map is then reduced to a one-dimensional map, involving the return time between successive visits to the Poincaré surface.
These standard techniques in the contemplation of homoclinic systems are then extended to a class of partial differential equations, on unbounded domains. This follows a method introduced by Fowler [Stud. Appl. Math. 83 (1990), pp. 329–353]. This extension involves more technicalities than in the case of ordinary differential equations.
The method of Fowler is extended to cover the case of vector-valued partial differential equations, and to consider the consequences of symmetry invariances. A Poincaré map is derived, and then is reduced to a finite-dimensional map. This map has dimension equal to the number of symmetry invariances of the system.
Some simple examples of this finite-dimensional map are studied, in isolation. A number of interesting bifurcation pictures are produced for these simple examples, involving considerable variation with the values of coefficients of the map.
Partial differential equations on finite domains are then considered, yielding similar results to the ordinary differential equation case. The limit as domain size tends to infinity is examined, yielding a criterion for distinction between the applicability of finite and infinite domain results.
Finally, these methods are applied to the Ginzburg-Landau system. This involves the numerical calculation of coefficients for the finite-dimensional map. The finite-dimensional map thus derived supports an interesting interlocked isola structure, and moreover correlates with numerical integration data.

Advisor: Fowler, A
Collisional and photoexcitation of transition metal clusters

The properties of transition metal clusters differ from those of both atomic and bulk size regimes. Such clusters are incompletely understood and potentially useful, making them attractive targets for further study.
The very smallest clusters studied in this thesis (CuO, Cu2 and Cu3) have been investigated with velocity map imaging. 1+1' photodissociation of CuO X 2Π3/2 was observed, via the C, D, E, F and H states of CuO. CuO&ast; was photodissociated to form Cu(2D3/2) + O(1D2). D0(CuO) was determined to be 3.041±0.030 cm-1. Non-resonant three-photon Cu2 photodissociation occurred throughout the energy range studied to produce one ground-state and one highly-excited copper atom,Cu&ast;. Cu&ast; was ionised by a single additional visible photon. Nearly all Cu&ast; atoms with internal energies between 41000 and 53000 cm-1 were observed. D0(Cu2) has been calculated to be 1.992±0.037 eV.
Features arising from photodissociation of Cu3 were observed in the Cu&plus; and Cu2&plus; ion yield spectra and images. Their structure was ill-resolved due to uncertainties in the internal energy of both parent Cu3 and product Cu2. These features correspond to single-photon dissociation of Cu3 to produce metastable D-states of the copper atom and vibrationally excited Cu2. One series of features implies a previously-unobserved state of either Cu2 or Cu3.
RhnN2O&plus; and RhnON2O&plus; (n=5, 6) were collisionally activated in collision-induced dissociation (CID) experiments with Ar and 13CO. These experiments were carried out in a Fourier Transform Ion Cyclotron Resonance(FT-ICR)spectrometer. Argon collisions induced both N2O desorption and N2O reduction. The branching ratios observed reproduced those seen in prior IR-MPD experiments. 13CO was observed to chemisorb to the cluster upon collision, activating not only N2O desorption and reduction but also CO oxidation. Formation of CO2 was noted to be particularly rapid on the n=5 cluster compared to the n=6 cluster.
Reactions of RhnN2O&plus; (n=4-6) clusters were also activated by black body radiation. This technique is known as BIRD - black-body induced infrared radiative dissociation. These studies revealed that the N2O desorption barrier exceeds the N2O reduction barrier on all clusters studied, but that the entropic favourability of desorption increases its rate relative to reduction with increasing cluster internal energy. The BIRD rate was much reduced upon cooling the ICR cell to 100 K. A further test of the BIRD mechanism increased the number of N2O ligands and hence the absorption rate. An approximately linear increase in the dissociation rate of Rhn(N2O)m&plus; was observed with index m. Deviations from linearity were caused by variations in the N2O desorption rate. In the case of Rh5(N2O)m&plus;, desorption rates corresponded closely to N2O binding energies calculated by density functional theory. The system was modelled using a master equation approach.

Keywords: transition metal cluster copper Cu rhodium Rh DFT
Advisor: Mackenzie, S
Approaches to the synthesis of non-natural carbohydrates via silicon tethered ene and allyl transfer reaction

The efficiency of an intermolecular synthetic transformation can be improved by temporarily linking reaction components together. The addition of a tether leads to enhanced regio- and stereocontrol by restraining the mobility of the reacting partners, effectively transforming an intermolecular reaction into its intramolecular counterpart. Silicon tethers are associated with an expanding range of applications, including hydrosilylations, cycloadditions and radical reactions. This project has continued work pioneered by the Robertson group into silicon tethered Type I ene cyclisations, extending the methodology to incorporate O-linked ene precursors with the intention of applying this chemistry to the stereoselective synthesis of non-natural carbohydrates.
This investigation encompassed advances in the area made concurrently within the Robertson group and extended the scope of the ene protocol by successfully incorporating latent functionality into the R-group side chain. In addition, a new route to the O-linked ene precursors was established employing silylcyanohydrin chemistry. In general, the ene reactions proceeded stereoselectively to generate the expected oxasilacyclohexanols, which could be cleaved oxidatively to afford 1,2,4-triols. The formation of the major diastereomer was consistent with ene cyclisation proceeding through a trans-decalin type transition state (e.g. leading to compound 1).
During our attempts to effect ene cyclisation in the O-linked prenyl systems we observed an unexpected side reaction, resulting from intramolecular allylic transfer. Further studies revealed that this novel process could be initiated thermally to generate 1,2-homoallylic diols with excellent levels of stereoselectivity. Tethered E- and Z-crotylsilanes were found to be equally receptive to this process.
Although attempts to apply the silicon tethered allyl transfer chemistry to aldimines and glycosides failed, an extension of the methodology to incorporate cyclohexadienylsilanes was successful and provided interesting synthetic intermediates for elaboration to carbasugars.

Advisor: Robertson, J
Complications and failures of secondary prevention in acute ischaemic  stroke

Stroke is a leading cause of death and the most common cause of disability in adults in the United Kingdom. Several treatments are effective in preventing stroke in the long term after TIA and minor ischaemic stroke, including aspirin, other antiplatelet agents, and blood pressure lowering drugs, statins and anticoagulation in atrial fibrillation. However, failure of secondary prevention to prevent recurrent vascular events is still a major clinical problem, as is the risk of bleeding associated with antiplatelet agents and anticoagulants.
This thesis determines the risks associated with urgent secondary prevention in the acute phase after TIA and minor stroke, particularly the reduction in risk of early recurrent stroke, the risk of bleeding with combination of aspirin and clopidogrel in the acute phase and whether or not there is a rebound increase risk of ischaemic stroke or recurrent TIA after withdrawal of a short course of clopidogrel.
I have shown that urgent and early treatment of ischaemic stroke with secondary prevention leads to an 80% reduction in recurrent stroke. I have also shown that an increased bleeding risk exists among aspirin naïve patients treated with combination antiplatelet medications compared to those already treated with aspirin. My work has also shown that discontinuation of clopidogrel following treatment for 30 days or more does not lead to a rebound increase in ischaemic stroke.
Bleeding events are a frequent complication of antiplatelet treatment in TIA and ischaemic stroke. I have shown that the long term risk of bleeding in a population study treated with antiplatelets is 6% per 100 person years. Using this information I identified risk factors for bleeding to develop a clinical baseline bleeding model to identify those at higher risk of bleeding. Age was identified as a significnant risk factor for both bleeding and recurrent ischaemic risk. In addition, bleeding events are associated with higher rates of fatality and disability in the older population.
Finally, I have shown that the time trends in stroke recurrence differ depending on the presenting event i.e TIA or stroke. Stroke recurrence risk after minor stroke is delayed compared with TIA, and remains high during the late phase despite current best medical treatment. Blood pressure control and atrial fibrillation are risk factors for late stroke recurrence identifying the unmet need for better detection and treatment potentials to reduce late recurrent stroke.

Keywords: secondary prevention
Stroke
Advisor: Rothwell, P
The non-linear optical properties of crystals and molecules

We consider some of the factors which affect the magnitudes of the tensor coefficients describing the nonlinear optical effects of second-harmonic generation and the Pockels or linear electro-optic effect. The effects of molecular geometry are our particular concern. The electro-optic coefficients of double sulphates with the langbeinite structure are compared with those of tetragonal phosphates and arsenates by ascribing the nonlinearitiee to the XO4 tetrahedra. The unfavourable orientation of the SO4 groups is shown to be responsible for the low electro-optic coefficients of the langbeinites.
These ideas are carried a stage further by assigning the nonlinearities to individual bonds. By this means the signs and magnitudes of the second-harmonic generation coefficients of several niobates are predicted from those of lithium niobate. Similar calculations are carried out for iodates, and empirical nonlinear optical bond polarisabilities are evaluated for a number of complex materials containing covalently bonded oxygen atoms. It is shown that the nonlinear polarisability depends on the electronegativity difference between the atoms forming the bond, and on their coordination.
A further chapter uses the well-known anharmonic oscillator model to establish a connection between nonlinear optical effects and optical activity in crystals of sodium chlorate and sodium bromate.

Advisor: Robinson, F
Cooperating to compete: the role of regional powers in global nuclear governance  

This thesis explores the role of regional powers in the development of regional nuclear regimes. Its central argument is that the devise of regional nuclear regimes through the leadership of regional powers is driven by both functional and strategic reasons. Functionally, regional nuclear institutions serve to provide more tailored solutions to respond to nuclear risks emerging at the local level. Strategically, the formation of sub-global institutions enables regional powers to exercise considerable influence on nuclear governance processes at both regional and global levels. And in situations where regional powers are dissatisfied with the global nuclear-institutional status quo, regional nuclear institution-building provides an incomparable opportunity to question that status quo and challenge, albeit indirectly, the preferences of the United States, their main architect.
The type of leadership provided by regional powers in the establishment of regional nuclear regimes is affected dynamically by two relationships: the regional powers' relation with the United States and their relation with secondary regional players. The former relation is defined as 'global nuclear alignment' and refers to the degree of proximity of the regional power towards U.S. nuclear preferences. The latter is defined as 'regional embeddedness' and captures the degree of convergence of regional powers' nuclear preferences with those of its most proxy regional contender, as well as the level of commitment shown by the regional power vis-à-vis regional integration.
The thesis argues that when both relations are low, divergence of the regional nuclear regime from global nuclear institutions is most acute. Conversely, when only one of the relations is high, the regional nuclear regime tends to converge with global nuclear institutions, either in goals or in methods. The theoretical framework is applied to investigate three cases of regional leadership as provided by Brazil, Indonesia and France in the establishment of the regional nuclear regimes in their respective regions.

Keywords: Regional Powers
Nuclear Policies
Global Order
Nuclear Order
Advisor: Betts, A
Hurrell, A
Non-invasive associative plasticity induction in a cortico-cortical pathway of the human brain

Associative plasticity, which involves modification of synaptic strength by coactivation of two synaptic inputs, has been demonstrated in many species. Here I explore whether it is possible to induce associative plasticity within a corticocortical pathway in the human brain using a novel protocol that activates two brain areas repeatedly with double-site transcranial magnetic stimulation (TMS). The pathway between ventral premotor cortex (PMv) and primary motor cortex (M1) which computes hand movements for precision grasp was manipulated.
First, I selectively potentiated physiological connectivity between the stimulated brain areas. The effects as assessed with paired-pulse TMS were in accordance with principles of spike timing-dependent plasticity (STDP), pathwayspecific and showed a different pattern of expression during rest and during performance of a naturalistic prehension task. Furthermore, I demonstrated that effects evolved rapidly, lasted for up to three hours and were reversible.
In a follow-up study, the protocol‘s effects on network interactions were investigated using functional magnetic resonance imaging (fMRI), specifically focussing on functional connectivity of network nodes within the wider parietofrontal circuit controlling reaching-and-grasping. The study demonstrated that functional connectivity was causally modified between stimulated nodes and that those changes in coupling also affected parallel, functionally-related pathways. Comparison of neurophysiological (paired-pulse TMS) and functional (fMRI) connectivity between individuals revealed a linear relationship of these connectivity indices; the first can assess the physiological nature of the interaction, whereas the latter can elucidate global network effects, making the techniques complementary.
Neurophysiological interactions of ipsilesional and contralesional PMv-M1 were tested in chronic subcortical stroke patients during grasping. Patients showed a diminished facilitatory influence of ipsilesional PMv on M1 compared to healthy controls which might contribute to their motor disability. Application of paired-associative TMS “normalised“ the reduced effective influence of ipsilesional PMv on M1 and this effect correlated with the patient‘s potential to improve their dexterity.

Keywords: hand function
neuroplasticity
neuroimaging
stroke
brain stimulation
connectivity
motor function
Advisor: Rushworth, MFS
The religious aspects of the Scottish covenanting armies, 1639-1651

While historians of Britain in the 1640s have long been attracted by the English New Model Army and in recent years by the English royalist armies, the armies fielded by the Scottish Covenanters have suffered a strange neglect. It was not until the work on this thesis was well- advanced that the crude nature of previous efforts became apparent. In an attempt to provide a basic understanding of the Covenanting forces, this thesis synthesizes a mass of material relating to the religious aspects of the armies. Two crucial questions emerged: did the military reflect Scottish society or any part of it; were the Covenanters' forces godly armies seeking to evangelize the areas they occupied? These themes have been interpreted broadly to include the rules of war, the army chaplains, religious manifestations in military life, the moral behaviour of the soldiers, and the role of the armies in spreading the presbyterian faith. In addition to those topics, an examination of the soldiers' relations with civilians and the political activities of the military have been included. The first most clearly allows one to determine whether the Covenanting armies attained the status of godly armies. The political question arises out of the close relationship between religious and political activities in the period. With the exception of family legal papers the entire spectrum of Scottish seventeenth-century sources was inspected. The records of the 1.Estates and its committees, the General Assembly and its Commission, form the basic sources for a view of national developments. At the local level the burgh, presbytery, family and kirk session records proved invaluable. Unfortunately few diaries, memoirs or letters survived. English materials primarily state papers, pamphlets and news books were also helpful. The findings of this thesis suggest that the armies of the Covenanters failed to achieve the ideals set for them.
Unfair prices in contracts in English and French law

When and why can parties escape from a contract on the ground that the price is unfair? This question is considered in a comparative and historical perspective in English and French law. The general rule in both systems is that the parties are free to determine the price and they are then bound by their contract. One well known exception in French law, which derives from Roman law, is Article 1674 of the Code civil which allows a vendor to rescind a contract for the sale of land if the price agreed in the contract is less than five-twelfths of the fair price. It is generally thought that there are no analogous rules in English law. However, the law on this subject is in fact considerably more complex and more colourful than this simple contrast would suggest.
Numerous rules on unfair prices in contracts were created in French law by the legislature and the courts since the promulgation of the Code civil in 1804. In English law, courts intervened in contracts on the ground of an unfair price in a few instances in the nineteenth century. However, only the rule on unfair prices in salvage contracts has survived until today. In both systems, the policies of preserving family wealth, protecting weak parties and giving special treatment to certain parties for economic, political, social or cultural reasons underpin these rules.
There are two principal conclusions. First, freedom of contract is much less extensive in French law than in English law. This is evident in the numerous rules on unfair prices in contracts in French law and in the primacy of the remedy of altering the price rather than rescission. Secondly, while in theory, French courts play a much less significant role than English courts in the development of law, the creation and abolition of certain rules on unfair prices in contracts by French courts shows that judicial creativity in French law can be much less constrained in practice than in English law.

Keywords: unfair prices
contracts
lesion
laesio enormis
salvage contracts
sale of reversions
Article 1674
Advisor: Whittaker, SJ