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

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.