Chemistry & Biochemistry Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2752
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Item Exploring Mechanisms and Predicting Reactivity of Transition Metal-Catalyzed and Photocatalyzed Radical and Polar Organic Transformations(2023) Martin, Robert Thompson; Davis, Jeffery; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The creation of protocols to form novel C-C and C-heteroatom bonds has been the primary goal of organic synthesis since its inception. Chemists have long harnessed both radical and polar reactivities, often as complementary paths to construct these bonds to yield more complex molecular architectures. However, compared to the development of synthetic protocols, development of mechanistic models and enriching of mechanistic understanding of many organic reactions has been limited. Computational studies into the mechanisms of organic transformations provide an avenue by which mechanisms of reactions can be better understood and new patterns of reactivity can be predicted. Herein, quantum-mechanical computational methods e.g., density functional theory (DFT) have been employed in the pursuit of understanding the mechanisms of a series of radical and polar reaction schemes. Specifically, DFT calculations were employed to understand the mechanism and origins of selectivity of two nickel(I)-catalyzed olefin functionalizations. These studies demonstrate a catalyst-control scheme by which selectivity can be induced by the steric properties of the catalyst (Chapter 1). Following this work, two photocatalytic transformations which yield difluorinated products were studied thoroughly with computations. First, a synthesis of difluorinated lactone derivatives revealed a long-lived radical intermediate and motivated mechanistic experiments to isolate this radical. Next, a synthesis of difluorinated oxindole derivatives demonstrated the ability of arenethiols to act as photocatalysts (Chapter 2). Then, computations were used to rigorously explore a copper-catalyzed reductive cross-coupling of imine and allenamides. Specifically, computations were employed to explore the mechanism of the transformation and the origins of stereoselectivity and the divergent formation of urea and diamine products (Chapter 3). Finally, two computational investigations into the mechanisms of transformations catalyzed by first-row transition metals are detailed. In particular, a nickel-catalyzed hydroarylation of gem-difluoroalkenes is explored computationally to determine the order of steps in the reaction. In addition, the mechanism of a cobalt(I)-catalyzed allylic substitution is considered to ascertain the nature of the transformation as either radical or polar (Chapter 4). Given the complexity of the mechanisms of these transformations, computational studies provide an alternative route to acquire useful mechanistic understanding that can support or explain observed experiments and suggest further mechanistic experiments that could provide stronger evidence for a given mechanistic proposal.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.