A palladium membrane reactor for organic transformations

Hydrogenation reactions are a widely-used class of catalytic transformations but the reactions require high-pressure H₂ gas and specialized equipment for safe handling. Hydrogenation with protons as a hydrogen source (electrocatalytic hydrogenation, ECH) overcomes this challenge but the substrate scope is limited to reactants that can be solubilized in protic conditions. In this thesis, a palladium membrane reactor is used to perform hydrogenation reactions with protons in any desired solvent. Palladium is semi-permeable for monoatomic, reduced hydrogen atoms so protons can be reduced at one side of the palladium, diffuse through the membrane and hydrogenate an unsaturated substrate on the other side of the palladium. The palladium membrane separates electrochemistry from hydrogenation, eliminating the solubility challenge of ECH. In this thesis, I first study hydrogen absorption into palladium. Hydrogen absorption is difficult to quantify because hydrogen is light and has minimal electron density. I demonstrate that coulometry can be an accurate technique to quantify hydrogen absorption when an electrochemical flow cell is used. The flow cell improves the selectivity of coulometry and enables quantification of absorbed hydrogen for a number of different palladium sample types. I then demonstrate the use of a palladium membrane reactor to pair two organic reactions together. Electrochemical reactions often form one product of value and one waste product. The palladium membrane acts as a dense barrier between the anode and cathode, enabling reaction of two organic substrates simultaneously. I also compare palladium membrane reactions to ECH reactions. I find that hydrogenation with a palladium membrane reactor increases reaction rates, changes the possible product distribution and lowers operating voltages. Finally, I study the use of the palladium membrane reactor for deuteration. Deuterated pharmaceuticals are of growing interest because of their increased half-lives. I find that the membrane reactor forms C–D bonds from an inexpensive and reusable D₂O starting material. The method has high site-selectivity and deuterium incorporations, and can be incorporated into a drug synthesis pathway.Science, Faculty ofChemistry, Department ofGraduat