Elucidation of Reactive Intermediates and Bonding in [4+1]-cycloadditions and Ionic Liquid Materials

Chemistry straddles the confluence of science and engineering, in that the hypotheses proposed, tested, and honed in the field cannot be fully divested from the utility of the knowledge gained for the application of those materials. For this work, two projects will be presented. First a series of studies involving [4+1]-cycloadditions will be presented wherein the outcomes were finely controlled through substrate design to establish the factors determining product formation for scaffolds useful in the development of small molecule pharmaceuticals. That series includes an investigation into the mechanism of cyclopropyl spirooxindole rearrangements wherein the determination of Hammett LFER plots elucidated a polar transition state for ketene substituted spirocyclopropanes, and a less defined mechanism for spirocyclopropyl isocyanates. Then the development of a [4+1]-cycloaddition strategy toward 1,5-dihydro-2H-pyrrol-2-ones from vinyl ketenes was established, though the steric sensitivity of the nitrene addition limited the substrate scope for this transformation. In the final section of the first project the development of a [4+1]-cycloaddition toward spirobenzofurans led us to delve into the composition of an intermediate oxyphosphonium enolate equilibria. To determine the relative composition of intermediate phosphonium species and the sensitivity of this cycloaddition to sterics and solvent, the off-target formation of epoxide dimers was studied via variable temperature NMR. A more complex mixture of oxyphospholenes and oxyphosphonium enolates and their correlating dimers were observed in a solvent stabilization and steric repulsion controlled equilibrium. Second, I will present my work probing the intermolecular bonding driving thermoresponsive ionic liquid phase separation, material properties leveraged for use in the fields of energy storage, desalination, separations, and refrigeration. Phosphonium ionic liquids with halogen or fluorinated anions were modified to probe the effect of chain length and anion size on their thermoresponsive phase separation in aqueous mixtures. Rather than size, the effective nuclear charge of the anion paired in balance with the hydrophobic pocket provided by the alkyl chain, to control the temperature and nature of IL phase separations. Then, systematic changes to phosphonium benzoate ILs were performed to isolate the contribution of H-bond directionality, ion pair strength, sterics, and pKa on water solvation through substitution of the benzoate anion with hydroxyl, carboxy, or sulfonyl functional groups. The systems in these studies have potential as pharmaceutical targets and scaffolds, or materials for energy storage and separations. In each case, the structural features of the molecules subjected played a crucial role in determining the product outcome, the reaction efficiency, and the material behavior.