Browsing by Subject "Kinetic Isotope Effects"
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Item Application of kinetic isotope effects and theoretical calculations to interesting reaction mechanisms(2009-05-15) Hirschi, Jennifer SueA variety of biological and organic reaction mechanisms are studied using powerful tools from experimental and theoretical chemistry. These tools include the precise measurement of kinetic isotope effects (KIEs) and the use of theoretical calculations to predict KIEs as well as determine factors that contribute to reaction acceleration and selectivity. Theoretical analysis of the Swain-Schaad relationship involves the prediction of a large number of isotope effects and establishes the semiclassical boundaries of the relationship. Studies on the mechanism of oxidosqualene cyclase involve the determination of a large number of precise KIEs simultaneously. Transition state models for the Sharpless asymmetric epoxidation have been developed that explain the versatility, high selectivities, and ligand accelerated catalysis of the reaction. Theoretical predictions on the proposed enzymatic mechanism of flavin dependent amine oxidation suggest a hydride transfer mechanism and rules out mechanisms involving covalent intermediates. Finally, a theoretical analysis of Diels-Alder reactions successfully describes the unexpected exo selectivity in some of these reactions.Item Mechanistic Investigation into the Sommelet-Hauser Rearrangement of an Allyl Ammonium Ylide Through Determination of 13C KIEs(2011-10-21) Collins, Sean ChristopherThe [2,3]-sigmatropic rearrangement is a pericyclic reaction of great synthetic utility to organic chemists. Within the scope of this reaction exist some cases in which the product corresponding to a [1,2] rearrangement is formed, despite the fact this is a forbidden process. Generally this is explained by a radical dissociation-recombination pathway; however, studies into the failure of transition state theory and the necessity to incorporate dynamic effects into mechanistic theory lead us to believe such products may arise from these phenomena. In particular, the possibility that many of these products result from an ?unsymmetrical bifurcating surface? in the potential energy landscape is intriguing. To investigate this possibility, the Sommelet-Hauser rearrangement of N-allyl-N,N-dimethylglycine methyl ester was explored. The combined use of experimental and theoretically predicted kinetic isotope effects (KIEs) has been previously shown to deliver great mechanistic insight into reactions. The combination of these techniques, however, has found little employ in studying [2,3] rearrangements. This combination was used to study this reaction, using the Singleton method for determining small heavy-atom isotope effects. Resulting experimental KIEs suggest the reaction proceeds by an asynchronous, concerted, early transition state, and is relatively exothermic. This agrees with previous studies and Hammond?s postulate. Predicted theoretical KIEs are in good agreement with experimental KIEs, and the associated transition structure confirms the results suggested by experiment. Interestingly, as calculations proceed from gas phase to solvent models, the activation barrier of the reaction increases, while its exothermicity decreases. The energy difference determined between the lowest and second lowest energy transition structures decreases to 0.81 kcal/mol in the PCM model, so we cannot exclude the contribution of this transition structure to the reaction. However, qualitative results from the associated KIEs and energetics are consistent with the lowest energy transition structure. This reaction does not seem to afford the [1,2] product, and most likely dynamic effects are insignificant in determining product distribution. However, the study has validated, with respect to this body of reactions, both the use of the Singleton method for KIE determination and the combination of these experimental and theoretical techniques.Item Mechanistic Investigations into the Origin of Selectivity in Organic Reactions(2009-05-15) Thomas, Jacqueline BesinaizDetailed mechanistic studies were conducted on several organic reactions that exhibit product selectivity (regio-, peri-, or enantioselectivity). The organic reactions studied were electrophilic aromatic substitutions, Diels-Alder cycloadditions of 1,3- dienes with cyclopentadieneone, Lewis acid catalyzed ene reactions with olefins, chlorinations of alkynes, and the enantioselective intramolecular Stetter reaction. Analyses of these systems were conducted by measurement of kinetic isotope effects, standard theoretical calculations, and in some cases dynamic trajectories. Mechanistic studies of electrophilic aromatic substitution, Lewis acid catalyzed ene reaction with olefins, the chlorination of alkynes, and the Diels-Alder cycloadditions of 1,3-dienes with cyclopentadienones, suggest that the origin of selectivity is not always a result of selectivity result from a kinetic competition between two closely related pathways to form distinct products. All of these systems involve one transition state on a potential energy surface that bifurcates and leads to two distinct products. In these systems, experimental kinetic isotope effects measured using natural abundance methodology, theoretical modeling of the potential energy surfaces, and trajectory analyses suggests that selectivites (regio- and periselectivities) are a result of influences by momenta and steepest-descent paths on the energy surface. The work here has shown that in order to understand selectivity on bifurcating surfaces, transition state theory is not applicable. In place of transition state energetics, the guiding principles must be those of Newtonian dynamics. In the mechanistic studies for the enantioselective intramolecular Stetter reaction, the origin of selectivity is a result of multiple transition states and their relative energies. Experimental H/D kinetic isotopes effects had lead to the conclusion that two different mechanisms were operating for reactions where carbenes were generated in situ versus reactions using free carbenes. However, 13C kinetic isotope effects and theoretical modeling of the reaction profile provide evidence for one mechanism operating in both cases.