The synthesis of heterocycles using radical intermediates has become an important area of research in recent years. The aim of our research was to develop radical methodologies to construct heterocycles on solid-support. Tri-cyclic benzimidazole derivatives are desirable synthetic targets with a range of biological activity and are part of certain anti-tumour agents. Solid-supported radical reactions with substituted benzimidazoles were performed under different experimental conditions, including different solvents, three different resins (Wang, Merrifield and Rink) and different radical reagents. 4-Mercaptobenzoic acid moiety served as a traceless linker in radical ipso-substitution reactions of benzimidazole precursors attached to solid-support to construct tri-cyclic and tetracyclic benzimidazole adducts. The solution-phase radical ipso-substitution protocol was quite successfully translated onto solid-support.

The work described herein is concerned with the [3+2] dipolar cycloaddition of amino acid derived azomethine ylids. Such cycloadditions are a highly efficient technique for the construction of proline derivatives, and may potentially be employed in other areas of asymmetric synthesis. Chapter 1 commences with a brief review of natural and synthetic, proline containing, molecules. Approaches to the synthesis of the proline moiety are described, focusing on previously developed methods for performing the [3+2] dipolar cycloaddition in a chiral manner. The methodology employed in this thesis is subsequently detailed, along with a brief description of the aims of the work. This is followed by a review of α-amino acid synthesis via chiral template technology. The potential application of chiral [3+2] dipolar cycloadditions to such syntheses is introduced. Chapter 2 describes the cycloaddition of carboxylate substituted chiral azomethine ylids with a range of dipolarophiles under both thermal and Lewis acid catalysed conditions. The effect on the stereoselectivity and yield caused by changing the conditions is discussed. Subsequent removal of the chiral template allows the synthesis of some tetra-substituted proline derivatives. Chapter 3 details the intramolecular variant of the cycloaddition. Further functionalisation of the cycloadducts via insertion of alternative chain links and sulfone alkylation was attempted. The Pummerer rearrangement of the related sulfoxide was shown to proceed smoothly and with total regio- and stereocontrol. Application of the methodology to the synthesis of a simple proline derivative and a symmetric pyrrolidine is described. Chapter 4 reports the attempted application of [3+2] dipolar cycloadditions to the synthesis of α-amino acids. The synthesis and subsequent cycloaddition of a new, α-amino acid derived, chiral template is described. Subsequent deprotection of the cycloadducts generated allows the synthesis of some α-phenyl substituted prolines. Unsuccessful attempts to incorporate additional substituents and perform the cycloaddition in an intramolecular manner are described. Chapter 5 contains a description of the techniques employed, together with spectroscopic data for the compounds described in this thesis.

The reaction of specially prepared salicylaldehyde benzyl ethers with the activated alkenes, methyl acrylate or acrylonitrile, in the presence of the catalyst, DABCO, has afforded Baylis-Hillman products, which have been subjected to conjugate addition with either piperidine or benzylamine. Hydrogenolysis of these conjugate addition products in the presence of a palladium-on-carbon catalyst has been shown to afford the corresponding 3-substituted coumarins, while treatment of O-benzylated Baylis-Hillman adducts with HCl or HI afforded the corresponding 3-(halomethyl)coumarins directly, in up to 94%. The 3-(halomethyl)coumarins have also been obtained in excellent yields (up to 98%) and even more conveniently, by treating the unprotected Baylis-Hillman products with HCl in a mixture of AcOH and Ac₂O, obtained from tert-butyl acrylate and various salicylaldehydes. The generality of an established route to the synthesis of coumarins via an intramolecular Baylis-Hillman reaction, involving the use of salicylaldehyde acrylate esters in the presence of DABCO, has also been demonstrated. Reactions between the 3-(halomethyl)coumarins and various nitrogen and carbon nucleophiles have been shown to proceed with a high degree of regioselectivity at the exocyclic allylic centre to afford 3-substituted coumarin products. The electronimpact mass spectra of selected coumarin derivatives have been investigated using high-resolution and B/E linked scan data. Fragmentation pathways have been proposed and fragmentation modes associated with different coumarin-containing analogues have been compared. A series of coumarin-containing analogues of ritonavir (a clinically useful HIV-1 protease inhibitor) have been prepared and characterized. The synthetic approach has involved the coupling of coumarin derivatives with a hydroxyethylene dipeptide isostere to afford ritonavir analogues containing coumarin termini. An interactive docking procedure has been used to explore the docking of ritonavir and a coumarincontaining analogue into the enzyme active site.

The reaction of various 2-nitrobenzaldehyde derivatives with methyl vinyl ketone (MVK) in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) has afforded the Baylis-Hillman adducts in moderate to good yield. Dissolution of the catalyst in the solvent before the addition of the aldehyde was observed to improve the yield. Reduction of the Baylis-Hillman adducts was effected by catalytic hydrogenation using a 10% palladium-on- carbon catalyst in ethanol to give quinoline and quinoline-N-oxide derivatives and, in some cases, acyclic reduction products. All products were characterised using NMR and, where appropriate, HRMS methods. Selected quinoline-N-oxides were successfully converted to their corresponding quinoline derivatives using phosphorus tribromide (PBr₃) and DMF as solvent. Conjugate addition of the benzylamine and piperidine nucleophiles to the Baylis-Hillman adducts was also investigated but proved problematic, with one of the substrates undergoing a retro-Baylis-Hillman reaction to afford the aldehyde in ca. 40% yield, but seemingly only traces of the required product. Perkin-type coupling of two 2-methylquinolines with benzaldehyde was successfully effected to afford the desired styrylquinoline derivatives confirming the potential of the Baylis-Hillman approach to the construction of the analogues of known HIV-1 integrase inhibitors. Three ¹³C NMR chemical shift prediction programmes, viz., Chem Window, neural network and HOSE (hierarchically ordered spherical description of environment) methods were applied to selected representative compounds prepared in the project. The results from the three programmes correlated reasonably well with the experimental carbon-13 chemical shift data for each of the selected compounds.

Baylis-Hillman reactions of 2,2’-dithiodibenzaldehyde with the acyclic alkenes, methyl vinyl ketone (MVK) and methyl acrylate have afforded the thiochromene derivatives in moderate yields, and this approach has been extended to the use of the cyclic alkenes, 2-cyclohexenone and 2-cyclopentenone to afford the tricyclic analogues. In all cases, reduction of the disulphide link and intramolecular cyclisation occurred in situ, and a preliminary kinetic study of this reaction using the acyclic substrates MVK and methyl acrylate was undertaken with the aim of elucidating the mechanism involved. The results obtained showed that the consumption of both 2,2’-dithiodibenzaldehyde and MVK and/or methyl acrylate followed 1st-order kinetics during the initial stages of the reaction, but then deviated from 1st-order linearity. The reaction with methyl acrylate was much slower than with MVK, and the kinetic data indicates the mechanism to be more complex than anticipated. Conjugate addition reactions of methyl acrylate-derived 2-nitrobenzaldehyde Baylis-Hillman adducts with the amines, piperidine and benzylamine, afforded a range of conjugate addition products as diastereomeric mixtures in excellent yield (80-100%). Catalytic hydrogenation of the conjugate addition products using a Pd-C catalyst in ethanol, has afforded the corresponding, novel 3-amino-2-quinolone derivatives in lower yield (22-37%).The application of [superscript 13]C NMR prediction programmes to selected compounds synthesized in this study has revealed reasonable correlations between the experimental and predicted values.

The preparation, characterization, and catalytic properties of some soluble and polymer-bound palladium and platinum complexes of ferrocene derivatives are described. Special emphasis has been placed on studies of the mixed "hard-soft" ligands such as PPFA and ISOPFA. [Formula Omitted] The soluble complexes (L-L)MC1₂ (L-L = BPPF, PPFA, ISOPFA, BPPFA; M = Pd, Pt) and [(L-L)PdS₂][C10₄]₂ (L-L = BPPF, PPFA; S = DMF, py) have been characterized by microanalyses, NMR and IR spectroscopic techniques. The cationic palladium(II) complex [(L-L)PdS₂][C10₄]₂ (L-L = PPFA, S = DMF) is an effective catalyst precursor for the hydrogenation of simple olefins at 30°C and 1 atm pressure. The rate of styrene hydrogenation depends on the substrate concentration, catalyst concentration and the solvent. The results are consistent with a homogeneous catalytic system. Platinum(II) complexes (L-L)PtCl₂ (L-L = (S,R)-PPFA, (S,R)-ISOPFA) are effective catalyst precursors for the hydrosilylation of aromatic ketones with Ph₂SiH₂. The complexes with mixed "hard-soft" ligands are better catalyst precursors than those with di(tertiary phosphine) ligands. Under the same conditions the hydrosilylation of ferrocenyl ketones results in further reduction and affords mainly the alkylferrocene products. The stable carbonium ion FcC⁺HCH₃ (Fc = Fe-(C₅H₅)(C₅H₄)-) is reduced by Ph₂SiH₂ to FcCH₂CH₃ in a thermal reaction which is catalyzed by the complex (PPFA)PtCl₂. The reaction of Ph₂SiH₂ with (L-L)PtCl₂ (L-L = PPFA, ISOPFA) yields a stable platinum(IV) hydride, which eliminates Ph₂SiHCl in solution to afford (L-L)PtHCl. The mechanistic implications of these observations are discussed. Polymers functionalized with ferrocene and ferrocene derivatives have been prepared. Mossbauer spectroscopic techniques and microanalyses are used to characterize these polymers and their palladium and platinum complexes. In a number of cases these results are confirmed by the cross-polarization/magic-angle spinning ¹³C NMR spectroscopic technique. The palladium(II) and platinum(II) derivatives of the ferrocenyl-amine and -phosphine containing polymers are effective catalysts for the hydrogenation and hydrosilylation of olefins. All the catalysts can be easily separated from the reaction mixture and can be recycled with no loss of activity. The pronounced effect of the attached ligand in the palladium based polymers indicates that free metal is not involved. However, in the case of platinum based catalysts, it is likely that reduction to platinum metal takes place. / Science, Faculty of / Chemistry, Department of / Graduate

This Ph.D. thesis deals with synthesis of monosubstituted cyclodextrin derivatives and investigating their properties. Alkylation of -cyclodextrin with allyl or cinnamyl bromide followed by peracetylation of remaining hydroxyl groups and separation of isomers resulted in the set of peracetylated 2I - O-, 3I -O- and 6I -O-alkylated cyclodextrins in up to 27% yields. Oxidative cleaveage of peracetylated allyl or cinnamyl derivatives resulted in a complete set of peracetylated 2I -O-, 3I -O- and 6I -O- formylmethyl or carboxymethyl derivatives which are useful precursors for preparation of regioselectively monosubstituted derivatives of -cyclodextrin. Moreover, a quick method to recognize single 2I -O-, 3I -O- and 6I -O- monosubstituted peracetylated cyclodextrins from each other using only 1 H NMR spectrum has been proposed. Ru-carbene complex catalyzed cross-metathesis of monoallyl -, -, and -cyclodextrins with perfluoroalkylpropenes resulted in the formation of the corresponding perfluoroalkylated cyclodextrins. The reactions proceeded under standard reaction conditions and the desired compounds were obtained in reasonable yields. Dynamic light scattering measurements proved the ability of the prepared compounds to aggregate in water solution forming nanoparticles in the range of tens and...

Midwest Independent Transmission System Operator, Inc. (MISO) is a non-profit regional transmission organization (RTO) that oversees electricity production and transmission across thirteen states and one Canadian province. MISO also operates an electronic exchange for buying and selling electricity for each of its five regional hubs. MISO oversees two types of markets. The forward market, which is referred to as the day-ahead (DA) market, allows market participants to place demand bids and supply offers on electricity to be delivered at a specified hour the following day. The equilibrium price, known as the locational marginal price (LMP), is determined by MISO after receiving sale offers and purchase bids from market participants. MISO also coordinates a spot market, which is known as the real-time (RT) market. Traders in the real-time market must submit bids and offers by thirty minutes prior to the hour for which the trade will be executed. After receiving purchase and sale offers for a given hour in the real time market, MISO then determines the LMP for that particular hour. The existence of the DA and RT markets allows producers and retailers to hedge against the large fluctuations that are common in electricity prices. Hedge ratios on the MISO exchange are estimated using various techniques. No hedge ratio technique examined consistently outperforms the unhedged portfolio in terms of variance reduction. Consequently, none of the hedge ratio methods in this study meet the general interpretation of FASB guidelines for a highly effective hedge. One of the major goals of deregulation is to bring about competition and increased efficiency in electricity markets. Previous research suggests that electricity exchanges may not be weak-form market efficient. A simple moving average trading rule is found to produce statistically and economically significant profits on the MISO exchange. This could call the long-term survivability of the MISO exchange into question.

No description available.

<p> New uranium(VI) complexes of a-hydroxyquinoline ligands of formulae U02(R-Q)2 R-QH have been prepared. In these compounds, the additional liquid is likely bonded as a zwitterion. Appropriate substitution in the 2- and 7-positions lead to interesting steric effects. Some uranium(VI) complexes reported in the literature have been re-examined and found to be incorrectly formulated. </p> <p> The scandium(III) complex of a-hydroxyquinoline obtained from aqueous solution was. found to be Sc(C9H6N0) 3 •H20 and not Sc(CgH&N0) 3 •C 9H7NO as previously reported. In the absence of water, Sc (CgH&NO) 3 •C 9H7NO 'Was obtained. New scandium(III) complexes of formulae Sc(R-Q) 3 •R-QH and Sc(R-Q) 3 •H20 have been prepared. </p> / Thesis / Doctor of Philosophy (PhD)