Christian, Chad F. (2007-05). The experimental and theoretical determination of combinatorial kinetic isotope effects for mechanistic analysis. Doctoral Dissertation. Thesis uri icon

abstract

  • Unfortunately, chemists can never experimentally unravel a full reaction pathway. Even our ability to define key aspects of mechanisms, such as short-lived intermediates and the even more ephemeral transition states, is quite limited, requiring subtle experiments and subtle interpretations. Arguably the most important knowledge to be gained about the mechanism of a reaction is the structure and geometry of the transition state at the rate-limiting step, as this is where a reaction's rate and selectivity are generally decided. The Singleton group has developed a methodology for predicting the combinatorial kinetic isotope effects (KIEs) at every atomic position, typically carbon or hydrogen, at natural abundance. A combination of experimental isotope effects and density functional theory (DFT) calculations has greatly aided our ability to predict and understand a reaction's pathway and transition state geometries. Precise application of this method has allowed for the mechanistic investigation of a myriad of bioorganic, organic, and organometallic reactions. The technique has been applied in the analysis of the catalytic borylation of arenes via C-H bond activation, dynamic effects in the enyne allene cyclization, palladium catalyzed allylic alkylation, the nature of proton transfer in orotate decarboxylase, and the epoxidation of enones with t-butyl hydroperoxide.
  • Unfortunately, chemists can never experimentally unravel a full reaction pathway.
    Even our ability to define key aspects of mechanisms, such as short-lived intermediates
    and the even more ephemeral transition states, is quite limited, requiring subtle
    experiments and subtle interpretations. Arguably the most important knowledge to be
    gained about the mechanism of a reaction is the structure and geometry of the transition
    state at the rate-limiting step, as this is where a reaction's rate and selectivity are
    generally decided. The Singleton group has developed a methodology for predicting the
    combinatorial kinetic isotope effects (KIEs) at every atomic position, typically carbon or
    hydrogen, at natural abundance. A combination of experimental isotope effects and
    density functional theory (DFT) calculations has greatly aided our ability to predict and
    understand a reaction's pathway and transition state geometries. Precise application of
    this method has allowed for the mechanistic investigation of a myriad of bioorganic,
    organic, and organometallic reactions. The technique has been applied in the analysis of
    the catalytic borylation of arenes via C-H bond activation, dynamic effects in the enyne
    allene cyclization, palladium catalyzed allylic alkylation, the nature of proton transfer in
    orotate decarboxylase, and the epoxidation of enones with t-butyl hydroperoxide.

publication date

  • May 2007