Biswas, Bibaswan (2015-08). Mechanistic Investigation of Rearrangement of Ammonium Ylides. Doctoral Dissertation. Thesis uri icon

abstract

  • A central aim of physical organic chemistry is the elucidation of reaction mechanisms. This knowledge is then usable in the rational control of reactions and the development of new synthetic methodology. A reaction mechanism is generally viewed as consisting of the sequence of intermediates and transition states connecting starting material and products, and it would be expected that any experimental observation can be understood from the mechanism. In this way, the applicability of transition state theory (TST) is an implicit assumption in the description of reaction mechanisms and particularly the understanding of rates and selectivity. However, TST sometimes fails to account for experimental outcomes. The main goal of this dissertation is to investigate mechanisms of reactions where ideas outside of TST are needed to explain observations. The origin of competing [2,3]- and [1,2]-rearrangements of ammonium-ylides was studied. The [2,3]-rearrangement is an allowed concerted pericyclic reaction while the [1,2]-rearrangement is forbidden and should occur by a stepwise process. The mechanism was investigated by a combination of experiments, standard theoretical calculations and dynamic trajectory calculations. The experiments include the measurement of kinetic isotope effects (KIEs), crossover experiments and temperature dependence of product ratio. The theoretical calculations predict an early and loose transition state for [2,3]-rearrangements. The theoretically predicted KIEs are in good agreement with experimental KIEs. Dynamic trajectories from an early and loose [2,3]-transition state showed that from a single transition state there is a bifurcation on the free energy surface. One of the paths is concerted that leads to [2,3]-rearrangment product. However, an alternative path involving cleavage leads to diradicals that can recombine to give both [1,2]- and [2,3]-products. This partitioning of dynamic trajectories was supported by the crossover experiment because the [2,3]-product showed less crossover compared to the [1,2]-product. Although the concerted path has an enthalpic advantage over the cleavage path, the cleavage path has an entropic advantage. This is supported by the fact that higher temperatures favored [1,2]-product. Since the competition of concerted [2,3]-rearrangement and bond cleavage observed experimentally is accounted for by the outcome of trajectories passing through the formal [2,3]-rearrangement transition state, we suggest here that the cleavage is facilitated by the pericyclic stabilization of the [2,3]-rearrangement transition state. Overall, we here propose that the common competition between the [2,3]- and [1,2]-rearrangement arises due to this dynamic effect. Dynamic trajectories from the formal [2,3]-rearrangement transition state leads to cleavage because the transitions state is early and loose. Stabilization of the ylides through hydrogen bonding shifts the transition state later. Therefore, the introduction of hydrogen bonding disfavors the cleavage from the formal [2,3]-transition state. This allowed us to control the competition.
  • A central aim of physical organic chemistry is the elucidation of reaction mechanisms. This knowledge is then usable in the rational control of reactions and the development of new synthetic methodology. A reaction mechanism is generally viewed as consisting of the sequence of intermediates and transition states connecting starting material and products, and it would be expected that any experimental observation can be understood from the mechanism. In this way, the applicability of transition state theory (TST) is an implicit assumption in the description of reaction mechanisms and particularly the understanding of rates and selectivity. However, TST sometimes fails to account for experimental outcomes. The main goal of this dissertation is to investigate mechanisms of reactions where ideas outside of TST are needed to explain observations.

    The origin of competing [2,3]- and [1,2]-rearrangements of ammonium-ylides was studied. The [2,3]-rearrangement is an allowed concerted pericyclic reaction while the [1,2]-rearrangement is forbidden and should occur by a stepwise process. The mechanism was investigated by a combination of experiments, standard theoretical calculations and dynamic trajectory calculations. The experiments include the measurement of kinetic isotope effects (KIEs), crossover experiments and temperature dependence of product ratio. The theoretical calculations predict an early and loose transition state for [2,3]-rearrangements. The theoretically predicted KIEs are in good agreement with experimental KIEs. Dynamic trajectories from an early and loose [2,3]-transition state showed that from a single transition state there is a bifurcation on the free energy surface. One of the paths is concerted that leads to [2,3]-rearrangment product. However, an alternative path involving cleavage leads to diradicals that can recombine to give both [1,2]- and [2,3]-products. This partitioning of dynamic trajectories was supported by the crossover experiment because the [2,3]-product showed less crossover compared to the [1,2]-product. Although the concerted path has an enthalpic advantage over the cleavage path, the cleavage path has an entropic advantage. This is supported by the fact that higher temperatures favored [1,2]-product.

    Since the competition of concerted [2,3]-rearrangement and bond cleavage observed experimentally is accounted for by the outcome of trajectories passing through the formal [2,3]-rearrangement transition state, we suggest here that the cleavage is facilitated by the pericyclic stabilization of the [2,3]-rearrangement transition state. Overall, we here propose that the common competition between the [2,3]- and [1,2]-rearrangement arises due to this dynamic effect.

    Dynamic trajectories from the formal [2,3]-rearrangement transition state leads to cleavage because the transitions state is early and loose. Stabilization of the ylides through hydrogen bonding shifts the transition state later. Therefore, the introduction of hydrogen bonding disfavors the cleavage from the formal [2,3]-transition state. This allowed us to control the competition.

publication date

  • August 2015