Graduation Year
2008
Document Type
Dissertation
Degree
Ph.D.
Degree Granting Department
Chemistry
Major Professor
Jon C. Antilla, Ph.D.
Committee Member
Kirpal Bisht, Ph.D.
Committee Member
Roman Manetsch, Ph.D.
Committee Member
Peter Zhang, Ph.D.
Keywords
aziridine, desymmetrization, catalysis, phosphoric acid, BrØnsted Acid, Mannich, enantioselective, asymmetric
Abstract
The synthesis of enantiomerically pure compounds is of vital importance. Most biologically active natural products are chiral and require asymmetric synthesis, chiral resolution, or the use of naturally chiral starting materials for their preparation. Organocatalytic enantioselective reaction methodology is a continuously growing area in organic chemistry. The use of organocatalysts as a potentially environmentally friendly alternative to metal catalysts is appealing to the pharmaceutical industry.
In this dissertation an enantioselective Mannich reaction using an organocatalyst was investigated. The reaction was between a ß-keto ester and an imine electrophile catalyzed by vaulted biphenanthrol (VAPOL) phosphoric acid. The reaction resulted in products with high yields, but low to moderate enantioselectivity and diastereoselectivity.
The development of the first Brønsted acid-catalyzed desymmetrization of meso-aziridines was also investigated. This is one of the first instances where a phosphoric acid has been used to catalyze a reaction that did not involve an imine. It was shown that the chiral VAPOL phosphoric acid was an excellent catalyst for the reaction resulting in high yields and enantioselectivities for the chiral ring opened products. It was also shown, for the first time, that a vaulted binaphthol (VANOL) phosphoric acid can also catalyze the ring-opening of meso-aziridines with comparable results to the VAPOL phosphoric acid in some cases. Mechanistic NMR studies were used to probe the reaction, and it is believed that evidence leads one to conclude that a unique mechanism for phosphoric acid-catalysis is followed. The products that can be obtained from this reaction, 1,2-diamines, are of high value for synthetic chemists. They have been used as chiral auxiliaries, ligands, and precursors to natural products.
Scholar Commons Citation
Rowland, Emily Bretherick, "Enantioselective Brønsted Acid-Catalyzed Reaction Methodology Part A: Enantioselective Mannich Reaction Part B: Enantioselective Desymmetrization of meso-Aziridines" (2008). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/482
