UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a given thesis/dissertation in DRUM.
More information is available at Theses and Dissertations at University of Maryland Libraries.
Browse
4 results
Search Results
Item AB INITIO MODELING OF THE SELECTIVITY AND REACTIVITY OF BOTH THERMAL AND LIGHT MEDIATED ORGANIC AND ORGANOMETALLIC TRANSFORMATIONS(2022) Dykstraa, Ryan Henry; Gutierrez, Osvaldo; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The mechanism of a reaction is the collection of events that take place that lead to the products of a chemical transformation. Though there are some events in a chemical reaction that can be observed by experiment, such long-lived intermediates, many of the events are too short lived to be measured. Due to these restrictions and the advancements in the development of moderately scaling computational tools, it is becoming commonplace to use quantum mechanical software packages to model the mechanism of a reaction. Here, I used quantum mechanical calculations alongside experimental evidence provided by multiple collaborators to understand the reactivity of both heat- and light-mediated organic transformations. In chapter 2, I investigated the role of electron donor-acceptor complexes in the generation of alkyl and acyl radicals in the presence of visible light. In addition, the pathways to the experimentally observed products, alkyl and acyl thioethers, were modeled. The lowest energy pathway to product, post-radical generation, was radical addition to the radical electron donor-acceptor complex. For a photoredox-catalyzed method to cyclopropanes from a novel halomethyl radical precursor (Chapter 3), computations strongly supported a redox-neutral reductive radical/polar crossover mechanism over radical pathways, consistent with experimental trends. Investigation of the isomerization of cinnamyl chloride to cyclopropane via a commonly used photoredox catalyst (Chapter 4) revealed that the reaction was mediated via dexter energy transfer between photocatalyst and substrate over the more commonly proposed electron transfer, affording diastereoselective product formation. A dual nickel/photoredox-catalyzed coupling of sulfinate salts and aryl halides gave a mixture of aryl sulfide and aryl sulfone products (Chapter 5), suggesting that disproportionation of sulfone radical was leading to the formation of thiyl radical. Modeling the product determining steps indicated that the product distribution was controlled by radical addition of the thiyl radical to the nickel(II) species versus reductive elimination of the sulfone bound to the nickel(III) catalyst. A bicyclo[1.1.1]pentane diborylated with pinacolboryl groups, one at the arm and head position, was found to have reactivity only at the bridgehead position (Chapter 6). Calculations of a hydrozone coupling reaction performed by the Qin group found that the reactivity was due to the unique hybridization of the bridgehead position as well as increased steric interactions at the arm position. Finally, a sulfoxide synthesized from a sulfinate salt could be activated with Grignard reagent, affording coupling of the substituents originally bound to the sulfoxide. DFT calculations validated the role of the sulfurane intermediate acting as a mediator to the coupled product.Item Early Transition Metal Studies of Dinitrogen Cleavage and Metal-Nitrogen Bond Reactivity Towards Catalytic N2 Fixation(2015) Keane, Andrew John; Sita, Lawrence R.; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The development of energy efficient catalysts that provide a range of commodity chemicals derived from the fixation of N2 is a highly attractive target due to the abundance of molecular nitrogen present in Earth’s atmosphere. Studies have focused on the systematic investigation of several key components of metal-catalyzed N2 fixation that detail molecularly discrete transformations involving the activation of N2, cleavage of the strong N≡N triple bond and N-atom functionalization to provide ammonia and other organic molecules of scientific and industrial interest. To this end, an evaluation of group 5 N2 cleavage using the pentamethylcyclopentadienyl, amidinate (CPAM) ligand framework that includes extensive kinetic and mechanistic investigations detailing the N-N cleavage reaction coordinate has been undertaken. Further studies conducted within group 5 include the synthesis and reactivity of tantalum imido complexes to elucidate metal-nitrogen bond reactivity and N-N cleavage relevant to the Chatt cycle. In group 6, photolytic N-N cleavage has been further investigated. Most notably, chemistry has been discovered for N2-derived metal nitride complexes of Mo and W that gives access to imido complexes capable of participating in nitrene group transfer (NGT) to carbon monoxide and isocyanides to provide isocyanates and carbodiimides respectively. For the first time, it has been demonstrated that imido complexes that participate in NGT chemistry can be derived from N2 to provide N-C based organic products. Collectively, these results serve to establish a new platform for studying the catalytic viability of the discovered transformations.Item Mechanism and Chance: Toward an Account of Stochastic Mechanism for the Life Sciences(2014) DesAutels, Lane Thomas; Darden, Lindley; Philosophy; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In this dissertation, my aim is to develop some important new resources for explaining probabilistic phenomena in the life sciences. In short, I undertake to articulate and defend a novel account of stochastic mechanism for grounding probabilistic generalizations in the life sciences. To do this, I first offer some brief remarks on the concept of mechanism in the history of philosophical thought. I then lay out some examples of probabilistic phenomena in biology for which an account of stochastic mechanism seems explanatorily necessary and useful: synaptic transmission in the brain, protein synthesis, DNA replication, evolution by natural selection, and Mendelian inheritance. Next, I carefully examine the concept of regularity as it applies to mechanisms--building on a recent taxonomy of the ways mechanisms may (or may not) be thought to behave regularly. I then employ this taxonomy to sort out a recent debate in the philosophy of biology: is natural selection regular enough to count as a mechanism? I argue that, by paying attention to the forgoing taxonomy, natural selection can be seen to meet the regularity requirement just fine. I then turn my attention to the question of how we should understand the chance we ascribe to stochastic mechanisms. To do this, I form a list of desiderata that any account of stochastic mechanism must meet. I then explore how mechanisms fit with several of the going philosophical accounts of chance: subjectivism, frequentism (both actual and hypothetical), Lewisian best-systems, and propensity. I argue that neither subjectivism, frequentism, nor best-system-style accounts of chance will meet all of the proposed desiderata, but some version of propensity theory can. Borrowing from recent propensity accounts of biological fitness and drift, I then go on to explore the prospects for developing a propensity interpretation of stochastic mechanism (PrISM) according to which propensities are (i) metaphysically analyzable and operationally quantifiable via a function of probability-weighted ways a mechanism might fire and (ii) not causally efficacious but nonetheless explanatorily useful. By appealing to recent analyses of deterministic and emergent chance, I argue further that this analysis need not be vulnerable to the threat of metaphysical determinism.Item PALLADIUM-CATALYZED ALLYLIC-ARYLATION: MECHANISTIC STUDIES AND APPLICATION TO THE TOTAL SYNTHESIS OF (+/-)-7-DEOXYPANCRATISTATIN DERIVATIVES(2009) Shukla, Krupa; DeShong, Philip; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Palladium-catalyzed carbon-carbon bond formation is one of the most widely used reactions for the synthesis of biologically active substances. The DeShong group has demonstrated that hypervalent silicates can be employed for allyl-aryl carbon-carbon bond couplings in the presence of a Pd(0) catalyst. The goals of this dissertation are (1) to demonstrate application of palladium-catalyzed allylic-arylation coupling to the total synthesis of (+/-)-7-deoxypancratistatin and its analogues, and (2) to study the mechanism of allyl-aryl cross coupling reactions. In spite of the potent antitumor and antiviral activity of (+)-7-deoxypancratistatin, the use of this compound is limited in clinical applications because of its low natural abundance and lack of a practical scalable synthetic route. In order to test the feasibility of siloxane-based coupling in the synthesis of 7-deoxypancratistatin, a simplified analogue of (+/-)-7-deoxypancratistatin was synthesized. The key reaction in the synthesis involved stereoselective construction of a carbon-carbon bond between A and C rings via coupling of an aryl siloxane with an allylic carbonate. While siloxane methodology was successfully applied to the synthesis of a (+/-)-7-deoxypancratistatin analogue, application of this methodology to the natural product (+/-)-7-deoxypancratistatin proved to be a significant challenge. To understand the causes of the failure of the coupling reaction, a detailed mechanistic study was undertaken. Hammett analysis of the allyl-aryl coupling reaction demonstrated that the rate of the coupling reaction was enhanced by electron-withdrawing groups on the aryl siloxane. The positive slope of the Hammett plot indicated a charged transition state in which negative charge on the aryl ring was stabilized inductively. Furthermore, this study provided useful information regarding the nature of ligands on the palladium. Based on this study, a new family of Pd(0) olefin catalysts was developed. These catalysts were found to be highly efficient and formed carbon-carbon bond even at ambient temperature. Novel Pd(0) olefin complexes were successfully employed in the synthesis of (+/-)-7-deoxypancratistatin. The key coupling reaction of allylic carbonate with aryl siloxane produced Hudlicky's intermediate, thus constituting formal total synthesis of the actual product. Though the reaction required higher catalytic loading and proceeded in moderate yields, the ability of the reaction to work at ambient temperature is advantageous for practical synthesis of the natural product. Future studies shall aim at optimization of the key coupling reaction and application of this methodology to the synthesis of pancratistatin and related derivatives.