NOVEL CATALYTIC METHODS OF C-O AND C-N BOND FORMATION 283 views

Nature has shown the ability to enzymatically synthesize molecules with remarkable chemo- and stereo-selectivity. Synthetic chemists have long sought to mimic this selectivity by developing methods that allow for late stage modification of molecular scaffolds. While there has been great headway made in this research, there is much room for improvement, thus we have developed methods of direct C-O and C-N bond formation with the aim of expanding the scope of synthetically accessible molecules. We have developed an organic iminium salt catalyzed nitrene-transfer aziridination of styrenes, with a substrate scope that was previously unachievable by other organocatalysts. In developing this method, we have gained valuable insight into the mechanism of nitrene-transfer by our iminium salt, thus allowing us to further our development of next generation catalyst design. The reaction is adaptable to tandem reactions, which is promising for the exploration of new reactivity. Our organocatalysis work is expanded further with the use of a dioxirane catalyst that can hydroxylate unactivated C-H bonds. This is the first example of a catalytically generated dioxirane that shows reactivity complementary to isolated dioxiranes. Furthermore, the mild reaction conditions used in the reaction allow for hydroxylation of molecules containing multiple functional groups. 6-membered N-heterocycles are commonly seen in pharmaceutical molecules, but have previously not been accessed using [n+1] cycloadditions. We have developed a novel, rhodium-catalyzed, aza-[5+1] cycloaddition to form tetrahydropyridines from vinylcyclopropanes. The reactions proceed with high regioselectivity, and allows for rapid access to substitution patterns on the pyridine that are currently not easily accessible.

PHD (Doctor of Philosophy)

English

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2020-12-08