Access Type
Open Access Dissertation
Date of Award
January 2018
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Chemistry
First Advisor
Jennifer L. Stockdill
Abstract
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.
Recommended Citation
Sirinimal, Mathes Hewage Hansamali Sakuntala, "Harnessing Radical Reactivity For The Construction Of Natural Product Frameworks And Transition Metal Catalyst Stability In A Modified Kochi Coupling Reaction" (2018). Wayne State University Dissertations. 2127.
https://digitalcommons.wayne.edu/oa_dissertations/2127