Date of Award
Fall 2022
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Miller, Scott
Abstract
The ubiquity of stereogenic elements both found in nature and encountered in our daily lives has necessitated the control of chirality in chemical synthesis. This dissertation describes the study of Brønsted acidic, Lewis basic and anion-binding catalysis, all moderated within organic chiral scaffolds to control different elements of chirality, including diastereoisomerism, point chirality and atropisomerism.In Chapter 2, BINOL and peptidic phosphoric acids were evaluated in the development of an atroposelective catalytic cyclodehydration to afford 1,2,4-triazoles, obtained with up to 88:12 er. The enantioenriched products obtained via chiral phosphoric acid catalysis were recrystallized and isolated as enantiopure samples, demonstrating the first asymmetric method to obtain chiral 1,2,4-triazoles. Observation of interesting substrate effects and determination of the absolute configuration of the major atropisomer led to mechanistic insights and a proposed enantioinduction model. Diastereo- and enantioselective alkene dichlorination was studied in Chapter 3. The Brønsted basic Dmaa peptides were repurposed to facilitate Lewis base catalysis in this electrophilic halogenation reaction. Control of the nucleophilic chloride addition, in hopes of influencing the reaction rate and diastereoselectivity, was attempted by exploiting the anion binding ability of ureas and thioureas. A urea-containing residue was developed and adapted to afford a bifunctional catalyst for this purpose. Chapter 4 discusses our contributions to the development of rapid optical assays to improve reaction screening process, in collaboration with the Anslyn Group at University of Texas, Austin. A novel covalent assembly that can report the enantioenrichment of a -stereocenter in a primary alcohol substrate was found to be a viable strategy for rapid report of ee in the dichlorinated allylic alcohols presented in Chapter 3. Additionally, the development of an ee-sensing assay for the chiral 1,2,4-triazoles described in Chapter 2 will enable further optimization of the atropisomeric triazole synthesis. Finally, synthesis of thiourea-containing peptide is disclosed in Appendix C. Preliminary evaluation of an anion-binding peptide catalyst demonstrated low level of enantioinduction in a reductive etherification reaction. In conclusion, this dissertation work employed several modes of asymmetric catalysis in controlling point or axial chirality to afford enantioenriched, structurally complex and medicinally relevant compounds.
Recommended Citation
Choi, Sooyun, "Investigation of Various Organocatalytic Modes in Asymmetric Transformations: Controlling Different Elements of Chirality" (2022). Yale Graduate School of Arts and Sciences Dissertations. 841.
https://elischolar.library.yale.edu/gsas_dissertations/841
