Access Type

Open Access Dissertation

Date of Award

January 2018

Degree Type


Degree Name




First Advisor

Jennifer L. Stockdill


Polycyclic N-containing heterocycles play an important role in therapeutic

applications and as molecular tools in studying biological processes, making them

important synthetic targets. Current synthetic approaches are too lengthy, use toxic

reagents or are limited to accessing a particular framework and hence, their synthesis

warrant further study. We have recently developed conditions to avoid both reduction and

slow addition in aminyl radical cyclizations in our venture to access the constrained ABC

core of calyciphilline A, a Daphniphyllum alkaloid. An electron deficient enone with a

pendent internal alkyne as the neutral aminyl radical precursor was used for radical

cyclization. Based on these results on enone reactivity we hypothesized that the rate of

the tandem cyclization over reduction can be significantly increased by introducing

electron deficient substituents on the olefin. This hypothesis was attempted on simple

substrates and to our surprise experimental data revealed that regardless of the presence

or absence of electron withdrawing substituents on the olefin, these work approximately

the same resulting similar yields. Cross coupling reactions using transition metals have played a vital role in the

synthesis of active pharmaceutical ingredients via C-C and C-heteroatom bond formation,

and has shown rapid advancements in the last few decades. While Pd is the most

predominantly used transition metal for cross coupling reactions, replacing Pd with nonprecious

metals to achieve similar reactivity is high in demand due to the many

advantages associated with the use of Pd. We took interest in exploring further into the

Cahiez-Fürstner modified Kochi Coupling reaction and were able to establish the largely

questioned stability of the iron catalyst, introduce a better alternative additive to enhance

reaction conditions and establish exclusive reactivity of Iron. We also demonstrated the

broad utility of these conditions on a wide substrate scope and conducted important

mechanistic experiments in efforts to understand the underlying mechanism.