Date of Award
Summer 2021
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
First Advisor
Clark, Joseph R.
Second Advisor
Yi, Chae
Third Advisor
Wang, Dian
Abstract
Transfer hydrogenation utilizes a non-H2 source of hydrogen to reduce double and triple bonds, utilizing transition metal catalysts in addition to some organocatalysts. The use of earth-abundant first row transition metals with ligands that fine tune the reactivity of the catalyst allows for the selective reduction of unsaturated functionalities by utilizing cheap and ubiquitous hydrogen sources such as water and various alcohols. This precludes the need for highly flammable H2 gas, which is often used with heterogeneous catalysts that offer limited selectivity and functional group tolerability. Catalysts optimized for the transfer hydrogenation of the desired functionality can be implemented to achieve the desired degree of reduction with high specificity. Currently, many methods for transfer hydrogenation rely on highly polarized -systems such as imines, ketones, and a,b-unsaturated ketones, and there are limited examples of transfer hydrogenation methods for the reduction of nonpolarized acetylenes. Herein, methods for the transfer hydrogenation of nonpolarized aryl alkynes will be described. To expand upon the novelty of the described transfer hydrogenation, a method for the incorporation of four deuterium in a single step by transfer deuteration was developed simply by substituting the hydrogen sources for their deuterated analogues. The recent FDA approval of the first deuterated drug molecule, Deutetrabenazine, has generated interest for the development of methods for the installation of deuterium, though isotopically labeled compounds have many uses across the field of chemistry including as analytical standards, mechanistic probes, and drug metabolism studies. In the context of pharmaceutical development, the selectivity of deuterium incorporation is extremely important, as isotopic impurities can diminish the overall therapeutic impact of a deuterated drug molecule. With this in mind, the methods for transfer hydrogenation and transfer deuteration were further developed to demonstrate the highly selective bisdeuteration of aryl acetylenes. In this work, I will describe my contributions to the development and scope of the transfer hydrogenation, transfer deuteration, and selective transfer hydrodeuteration of aryl alkynes.