The palladium-catalysed asymmetric allylic alkylation is a mild and versatile bond forming reaction between a nucleophile and allylic electrophile. The wide scope of nucleophiles used, and the high regio- and stereoselectivity obtainable renders this transformation an important technique in enantioselective synthesis. The mechanism is known to go via a key palladium π-allyl intermediate, followed by nucleophilic addition occurring at the terminal allylic carbon. Both the formation of the palladium π-allyl, and the nucleophilic addition to generate the alkylated product and palladium(0) proceed with high levels of inversion of stereochemistry, and both provide an opportunity for the induction of stereochemistry. However in the case of ligand controlled nucleophilic addition memory effects have been observed. The epimerisation of the palladium π-allyl before nucleophilic attack is key to achieving high levels of selectivity when racemic starting materials and chiral ligands are employed. Previous work in the Lloyd-Jones group has determined that prolonging the lifetime of the palladium π-allyl species, either by the use of weakly coordinating counter ions or slow addition of the nucleophile reduces this memory effect, however increasing the rate of epimerisation would have a result in a similar effect. One of the mechanisms resulting in the epimerisation of the palladium π-allyl species is mediated by palladium(0), however the details of the mechanism are not well understood. We describe the synthesis of a diastereotopic palladium cyclohexenyl ester and labelled the complex with 108palladium and d3 at the cyclohexenyl ester. Using simultaneous 31P NMR and mass spectrometry, we have acquired strong evidence against mechanisms involving a single electron transfer, as proposed by Stille, of formation of a dinuclear palladium(I) species followed by an inversion event, and we have gained evidence supporting the direct nucleophilic addition of the palladium(0), resulting in inversion of stereochemistry. The differences in rates of nucleophilic attack involving monodentate and bidentate phosphine ligands on both the palladium I-cyclohexenyl ester have also been explored. Throughout the mechanistic investigation, it was noted that the 31P NMR spectroscopy experiment used gave non-quantitative results, and in fact the differences in quantification of the species varied with the spectrometer used. We also describe our investigations into where these differences arise from and an optimum set of parameters for quantitative 31P NMR spectroscopy. The conclusions are also applicable to other heternuclear NMR spectroscopic experiments.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 189-196).

Benzylpenicillin was found to migrate irreversibly into human erythrocytes. No detectable amounts of penicillin bind to the erythrocyte membrane. After migration into the cell, benzylpenicillin is hydrolyzed into benzylpenicilloic acid, which can not migrate out of the cell. DNDS did not affect the appearance of benzylpenicilloic acid in the erythrocyte, therefore showing that: 1) benzylpenicillin does not hydrolyze to benzylpenicilloic acid in the incubation mixture then migrate to the cell, 2) benzylpenicillin migrates into the erythrocyte and is hydrolyzed to benzylpenicilloic acid. Benzylpenicilloic acid does not migrate into erythrocytes.Ball State UniversityMuncie, IN 47306

No description available.

Thesis (Ph. D.)--Institute of Paper Chemistry, 1972. / Includes bibliographical references (leaves 156-162).

No description available.

This thesis describes the application of (arene)Cr(CO)3 methodology to the Stereoselective and enantioselective synthesis of substituted arenes. Chapter one reviews the main methods of preparation and decomplexation of (arene)Cr(CO)₃ complexes and the electronic and steric influences of the Cr(CO)₃ unit on the arene. Chapter two demonstrates that the benzylic oxygen directing effect in complexation reactions operates via a direct oxygen bond to the incoming metal unit. Attachment of bulky ft-acceptor groups, such as t-butyldimethylsilyl, to the benzylic oxygen overrides this directing effect. Chapter three describes the regioselective Cl functionalisation of the cryptopine skeleton. Complexation of dihydrocrytopine gives only a single product, the relative configuration of the product being determined using an X-ray crystal structure analysis. Subsequent alkylation of the O-methyl derivative gives Cl alkylated products. Chapter four describes the regioselective ortho functionalisation of ephedrine and pseudoephedrine derivatives. Treatment of (1S,2R)-(N,O-dimethylpseudoephedrine) Cr(CO)₃ with n-butyllithium leads to exclusive removal of the pro-(R) ortho proton. The observed stereoselectivity arises via</em deprotonation from cyclic bidentate five-membered chelates. Chapter five describes the regioselective C4 and C5 functionalisation of (hydrocotarnine)Cr(CO)₃. Complexation of 1-methylhydrocotarnine occurs to give exclusively the exo-1-methyl derivative. Further functionalisation to give the 1,5- and 4,5-dimethyl products is also described. Chapter six describes the synthesis of ortho substituted (benzaldehyde)Cr(CO)₃ complexes. Chiral material is available via preferential kinetic hydrolysis of, or classical separation of, the L-valinol derived imines. Chapter seven describes the Stereoselective addition of nucleophiles to (o-anisaldehyde) Cr(CO)₃ and (o-trialkylsilylbenzaldehyde)Cr(CO)3. With (o-anisaldehyde)- Cr(CO)₃ the additions are completely stereoselective giving the (RR,SS) diastereoisomer. With (o-trialkylsilylbenzaldehyde)Cr(CO)₃ the ratio of products is influenced by the nature of Lewis acidic species present. Chapter eight describes the Stereoselective benzylic elaboration of (o-methoxybenzyl methyl ether)Cr(CO)₃ achieved via selective removal of the exo benzylic proton from transition states with the methoxy groups anti to each other.

A number of organometallic transformations related to proposed elementary steps in the reductive polymerization of carbon monoxide are discussed. The use of isonitrile as model ligands for carbon monoxide, with which they are isoelectronic, is proposed. Investigations show that alkyl migration to isonitrile is preferred over migration to carbon monoxide. Iminoformyl products due to hydride migration to isonitrile are not, however, observed. Syntheses of a range of cationic complexes of the type [ (η⁵-C₅H₅)M(L)₂(CNR)]⁺, [(η⁵-C₉H₇)Ru(L)₂(CNR)]⁺ and [(η⁵-C₉H₇)M(L)₂(CO)]⁺ (M = Fe, Ru; L = CO, phosphine) are described. In two cases, addition of hydride to the isonitrile cations is followed by protonation on work-up to give aminocarbene complexes. These are inert to further reduction under the conditions employed. The majority of isonitrile cations lose the isonitrile ligand to give good yields of metal hydride complexes. A mechanism involving ring-slippage of the hydrocarbon ligand is implicated. Hydride addition to η⁵-C₉H₇ complexes results, in the majority of cases, in loss of the hydrocarbon ligand from the complex and recovery of indane. Evidence for the intermediacy of metal formyl complexes in a number of hydride donation reactions is presented. These formyl complexes are formed from carbonyl hydride complexes either under moderate CO pressure or in THF solution. Hydride complexes lacking a carbonyl ligand are found to be inert. Finally, two reactions, one involving an alkyl migration reaction catalyzed by silver(I) salts, and the other involving the reduction of a metal acyl ligand to metal alkyl, are combined to demonstrate a model for carbon chain growth at a metal centre. The synthesis of an iron pentanoyl complex, followed by a decomplexation reaction, gives pentanoic acid in which all the catbon atoms are potentially directly derived from carbon monoxide. This is the first synthesis of a single homologous acid from carbon monoxide.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Vita. Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Les rodonticides anticoagulants (AR) sont utilisés depuis les années 40 pour lutter contre les rongeurs. Seulement quelques années après leur commercialisation des cas de résistances ont été décrits. Les mécanismes à l'origine de ces résistances sont relativement bien décrits chez le rat brun et la souris domestique mais très peu chez le rat noir. Une étude de terrain a permis de mettre en évidence 8 mutations codantes du gène Vkorc1 chez le rat noir responsable d'un possible phénotype résistant. Actuellement, les résistances concernent surtout les AR de 1ère génération. Ainsi, les AR de 2nde génération qui sont encore actifs chez les rongeurs résistants sont de plus en plus utilisés. Cependant, en raison de leur longue rémanence tissulaire, ils sont responsables de phénomènes d'intoxication de la faune non cible. Face à ce problème majeur, une nouvelle génération d'anticoagulants plus écocompatible doit être développée. Ce travail propose une méthode pour le développement d'une 3ème génération d'AR en retravaillant la 2nde génération via le concept de la stéréochimie. En effet, les AR de 2nde génération sont un mélange de diastéréoisomères qu'il est possible de séparer. Les propriétés biologiques et toxicocinétiques des diastéréoisomères de chacune des molécules actuellement sur le marché ont été étudiées. Systématiquement, l'un des deux couples de diastéréoisomères est éliminé beaucoup plus rapidement que l'autre. Ainsi, le développement d'appâts enrichis avec le couple de diastéréoisomères les moins persistants, permettrait de réduire les risques écotoxicologiques associés à leur utilisation / Anticoagulant rodenticides (AR) have been used since the 1940s to control rodents. Only a few years after their commercialization, cases of resistance have been described. The mechanisms responsible for these resistances are relatively well described in brown rats and domestic mice but approximately unknown in black rats. A field study performed in France and Spain revealed 8 coding mutations of the Vkorc1 gene in black rat populations responsible for a possible resistant phenotype to 1st generation ARs essentially, as described for other rodents. 2nd generation ARs still active in resistant rodents are thus increasingly used. However, due to their long tissue persistence, their use is associated with an increased risk of secondary poisoning of wildlife. Faced to this major problem, a new generation of more ecofriendly anticoagulants must be developed. This work proposes a method for the development of a 3rd generation of AR by revisiting the 2nd generation AR based on the stereochemistry. Indeed, 2nd generation ARs are a mixture of diastereomers that can be easily separated. The biological and toxicokinetic properties of the diastereoisomers of each of the molecules currently on the market have been studied. Systematically, one of the two pairs of diastereoisomers is eliminated much faster than the other. Thus, the development of baits enriched with the pair of less persistent diastereoisomers would reduce the ecotoxicological risks associated with their use