Doctor of Philosophy / Department of Chemistry / Christopher J. Levy / Stepped helical salen complexes with vanadium as the central metal were synthesized and characterized. The helicity in these complexes arise from the fused phenyl rings (phenanthryl and benz[a]anthryl) as sidearms, whereas the chirality arises from the chiral cyclohexyl diamine or binaphthyl diamine backbones. These complexes showed good yields and moderate enantioselectivity in asymmetric sulfoxidation reactions with methylphenyl sulfide as the substrate and H2O2 or cumene hydroperoxide as the oxidants. To further improve the closed nature of these complexes with a tetradentate salen ligand, we synthesized and characterized vanadium complexes with tridentate (S)-NOBIN backbone Schiff base ligands with phenanthryl and benz[a]anthryl as the sidearms. After initial catalytic study, we concluded that these catalysts are too open in nature to impose face selection during asymmetric induction. We also synthesized and characterized vanadium and titanium salan complexes. These complexes can adopt β-cis geometry, thereby making the complex “chiral at metal” and they are known for better catalysts in terms of asymmetric induction than their unreduced counterparts. However, these complexes showed better catalytic activity than their unreduced counterparts in sulfoxidation reactions with methylphenyl sulfide as the substrate and H2O2 or cumene hydroperoxide as the oxidants. We also put an effort to synthesize mixed salen complexes with vanadium as the central metal. These complexes have two different sidearms attached to one backbone unit. However, our method did not work well to produce pure mixed salen ligands. The catalysis results for mixed salen vanadium complexes are also comparable to the unreduced vanadyl salen complexes. Lastly, we synthesized and characterized new helical titanium Schiff base complexes with (S)-NOBIN backbone and phenanthryl and benz[a]anthryl sidearms. Single crystal studies showed that these complexes exist in the M helical conformation in the solid state. These complexes showed moderate activity in asymmetric aldol addition reactions between 2-methoxy propene and different aldehydes.

Doctor of Philosophy / Department of Chemistry / Christopher J. Levy / The helix is an important chiral motif in nature, there is increasing development in field of helical transition metal complexes and related supramolecular structures. Hence, the goals of this work are to apply the principles of helicity in order to produce metal complexes with predictable molecular shapes and to study their properties as asymmetric catalysts. Computational studies suggest that the (1R,2R)-cyclobutyldiamine unit can produce highly twisted salen complexes with a large energy barrier between the M and P helical forms. To test this prediction, the tartrate salt of (1R,2R)-cyclobutyldiamine was synthesized and condensed with a series of saliclaldehydes to produce novel salen ligands. The salicylaldehydes chosen have extended phenanthryl or benz[a]anthryl sidearms to encourage formation of helical coordination complexes. These ligands were metallated with zinc, iron and manganese salts to produce salen metal complexes which were characterized by NMR analysis, high-resolution mass spectrometry, and IR spectroscopy. A second ligand type, neutral bis(pyridine-imine) has also been synthesized from (1R,2R)-cyclobutyldiamine and quinolylaldehydes. The synthesis of bis(pyridine-imine) ligands was conducted using greener method, solvent assisted grinding. These ligands, in-situ with nickel metal salts, showed good catalytic activity for asymmetric Diels-Alder reactions. The third ligand type studied was chiral acid-functionalized Schiff-base ligands. These were synthesized by the condensation of 3-formyl-5-methyl salicylic acid and (1R,2R)-cyclobutyldiamine. With this type of ligand, there is possibility of producing both mono and dinuclear metal complexes. In our studies, we were only able to synthesize mononuclear complexs. These were tested as catalysts for asymmetric direct Mannich-type reaction, but were found to be ineffective.

No description available.

Dynamic kinetic resolution (DKR) is a powerful method for obtaining compounds with high optical purity. The process relies on the combination of a kinetic resolution with an in situ racemization. In this thesis, a combination of an immobilized hydrolase and a transition metal-based racemization catalyst was employed in DKR to transform racemic alcohols and amines into enantioenriched esters and amides, respectively. In the first part the DKR of 1,2-amino alcohols with different rings sizes and N-protecting groups is described. We showed that the immobilization method used to support the lipase strongly influenced the stereoselectivity of the reaction. The second part deals with the DKR of C3-functionalized cyclic allylic alcohols affording the corresponding allylic esters in high yields and high ee’s. The protocol was also extended to include carbohydrate derivatives, leading to inversion of a hydroxyl substituted chiral center on the carbohydrate. The third part focuses on an improved method for obtaining benzylic primary amines. By using a novel, recyclable catalyst composed of Pd nanoparticles on amino-functionalized mesocellular foam, DKR could be performed at 50 °C. Moreover, Lipase PS was for the first time employed in the DKR of amines. In the fourth part DKR was applied in the total synthesis of Duloxetine, a compound used in the treatment of major depressive disorder. By performing a six-step synthesis, utilizing DKR in the enantiodetermining step, Duloxetine could be isolated in an overall yield of 37% and an ee &gt;96%. In the final part we investigated how the enantioselectivty of reactions catalyzed by Candida Antarctica lipase B for δ-substituted alkan-2-ols are influenced by water. The results showed that the enzyme displays much higher enantioselectivity in water than in anhydrous toluene. The effect was rationalized by the creation of a water mediated hydrogen bond in the active site that helps the enzyme form enantiodiscriminating binding modes. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p>

In biological systems, most of the active organic molecules are chiral. Some of the main constituents of living organisms are amino acids and sugars. They exist predominantly in only one enantiomerically pure form. For example, our proteins are built-up by L-amino acids and as a consequence they are enatiomerically pure and will interact in different ways with enantiomers of chiral molecules. Indeed, different enantiomers or diastereomers of a molecule could often have a drastically different biological activity. It is of paramount importance in organic synthesis to develop new routes to control and direct the stereochemical outcome of reactions. The aim of this thesis is to investigate new protocols for the synthesis of complex chiral molecules using simple, environmentally friendly proline-based organocatalysts. We have investigated, the aziridination of linear and branched enals, the stereoselective synthesis of β-amino acids with a carbene co-catalyst, the synthesis of pyrazolidines, the combination of heterogeneous transition metal catalysis and amine catalysis to deliver cyclopentenes bearing an all-carbon quaternary stereocenter and a new heterogeneous dual catalyst system for the carbocyclization of enals. The reactions presented in this thesis afforded the corresponding products with high levels of chemo-, diastero- and enantioselectivity. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 5: Submitted. </p>

We present three models of the role of asymmetric information in environmental protection. Chapter one considers the market for a green credence good - a good whose environmental characteristics are not observed by the consumer, even ex post - in the presence of environmentally-conscious consumers. Producers may choose to advertise their products. However, if communication is not regulated it can degenerate into "cheap talk". We explore the scope for credible transmission of environmental information by green producers, and the limits on it. In Chapter two we develop some similar themes in an experimental setting, with the focus again on consumer reactions to producer-provided information on the environmental attributes of goods, and the potential role of government to improve social welfare by manipulating the use of certification. In Chapter three the focus is somewhat different, whilst maintaining the theme of the role of information asymmetries in an environmental policy setting. In the model here a regulator has to decide whether or not to regulate a polluting activity with imperfect information regarding the net benefits of so doing. In making her decision, the regulator can listen to an adviser, who may or may not be biased. We look at how the decision maker can exploit the advisories incentive to build reputation to achieve better decisions. As a whole the thesis further underscores and illustrates the critical role that availability and distribution of information plays in policy making aimed at environmental protection.

Developing asymmetric C-H bond activation methods in order to achieve enantiopure products is crucial for the advancement of the field and for the production of novel chiral compounds. Therefore, we tried to develop this area of organic chemistry by presenting metal catalyzed stereoselective C-H bond activation utilizing chelation-assisted tools. The first section of this study involves Rh(I) catalyzed asymmetric C-H bond activation of a series of ketones via an intermolecular procedure. By this method, we examine ortho-alkylation of aromatic ketones and β-functionalization of α-β unsaturated ketones with a series of prochiral olefins. In the second section, we present an efficient three steps method for stereoselective intramolecular C-H bond activation of indol-3-carboxaldehyde with tethered prochiral olefins. The catalytic system in both methods involves a joint chiral primary amine and Rh(I) catalyst. Chiral primary amines can serve to induce enantioselectivity as well as acting as a useful directing group which has shown appropriate coordination to the transition metal catalyst, providing high regioselectivity. / February 2017

Approved for public release; distribution is unlimited / In the wake of the September 11, 2001 attacks, the issue of political violence expressed via mass destruction has raised security concerns to an unprecedented degree not seen since the end of the Cold War. As a principal adversary, the Soviet Union has been replaced by terror networks applying asymmetric warfare to achieve politically charged or ideologically driven objectives. A scenario whereby non-state actors would acquire a nuclear capability not only threatens the security of the United States, but would destabilize the Westphalian notion of the primacy of nation-states within the international system. Despite U.S. expenditures of over $86 million to help nearly 30 countries worldwide in preventing the smuggling of weapons-useable radiological materials, over 20 known cases of such activity were reported between 1992 and 2001. Previous research has concentrated on a singularly defined threat: The Rogue State. Today's challenges are characterized by more defused, decentralized networks, to include transnational actors with the potential to proliferate and supply terrorists with a nuclear weapon or weapons-grade radiological material. This thesis examines the applicability of traditional Cold War strategies such as deterrence, pre-emption, prevention, and coercive diplomacy in the present context, to deny extremist groups and associated networks the means to buy, steal, or make nuclear and radiological weapons. This thesis proposes a multi-dimensional approach in support of mixed-strategies for winning the race against nuclear terror. The author contends that terrorist groups cannot acquire nuclear or radiological technology without the witting or unwitting support of state actors.

The research presented in this thesis is a project funded by the EU-network of the Marie Curie project NANO-HOST in collaboration with partner institutes. The aims of this network are to develop innovative methods for the preparation, recovery and reuse of single-site, nanostructured catalytic materials, and further on apply them in combination with specifically engineered reactors for a sustainable production process for making high value fine chemicals. One part of this project was to prepare chiral diphosphine ligands and their complexes for currently challenging reactions, such as asymmetric carbonylations (homogeneous catalysis). Catalytic studies of these chiral diphosphine ligands were carried out in asymmetric hydroxy-and alkoxy-carbonylations and hydrogenation reactions. The second part of this project was the heterogenisation of these chiral homogeneous complexes through collaborations with the network partners and furthermore their catalytic behavior was studied.

The aim of this project was to utilize chiral cation-directed catalysis in the asymmetric synthesis of novel hererocycles. This goal was initially realized by the synthesis of azaindolines in high yields and enantioselectivities (Chapter 2). Extension of this methodology to substrates bearing two stereogenic centres was successful, although control over both diastereoselectivity and enantioselectivity in this process was modest. Finally the synthesis of heterocycles utilizing cation-directed rearrangement processes was examined, with proof of concept obtained for a novel asymmetric cyclization to form xanthenes.