Catalytic Enantioselective Cation Radical-Mediated Transformations: A New Paradigm in Asymmetric Catalysis The major goal of this research endeavor is to develop new catalyst systems for selective organic transformations that will be broadly applicable to the synthesis of therapeutically relevant small organic molecules. Specifically, our research is focused on developing new practical chemical reagents for the asymmetric catalysis of radical processes in an operationally trivial manner. We will develop moisture and oxygen stable chiral organic single-electron oxidation catalysts that are activated by visible light in order to initiate chemical reactivity. We will demonstrate that our catalysts can be utilized in enantioselective transformations mediated by cation radical species. It is anticipated that reactions such as enantioselective cycloaddition and alkene hydrofunctionalization reactions will be possible and will provide biomedical researchers with additional practical tools for single enantiomer medicinal agent synthesis. The proposed transformations follow the desirable tenants of atom economy, waste reduction and overall redox neutrality. As a consequence, we expect that this catalyst system could provide economic benefits in regards to the production of medicines available to the general public.

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Catalytic Enantioselective Cation Radical-Mediated Transformations: A New Paradigm in Asymmetric Catalysis The objective of this research program is to invent new synthetic protocols of relevance to the preparation of medicinal agents.
We aim to develop catalysts that absorb visible light to promote reactions that are otherwise outside of the scope of existing chemical transformations.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Synthetic and Biological Chemistry A Study Section (SBCA)
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Lees, Robert G
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University of North Carolina Chapel Hill
Schools of Arts and Sciences
Chapel Hill
United States
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Griffin, Jeremy D; Cavanaugh, Cortney L; Nicewicz, David A (2017) Reversing the Regioselectivity of Halofunctionalization Reactions through Cooperative Photoredox and Copper Catalysis. Angew Chem Int Ed Engl 56:2097-2100
Morse, Peter D; Nicewicz, David A (2015) Divergent Regioselectivity in Photoredox-Catalyzed Hydrofunctionalization Reactions of Unsaturated Amides and Thioamides. Chem Sci 6:270-274
Griffin, Jeremy D; Zeller, Mary A; Nicewicz, David A (2015) Hydrodecarboxylation of Carboxylic and Malonic Acid Derivatives via Organic Photoredox Catalysis: Substrate Scope and Mechanistic Insight. J Am Chem Soc 137:11340-8
Romero, Nathan A; Nicewicz, David A (2014) Mechanistic insight into the photoredox catalysis of anti-markovnikov alkene hydrofunctionalization reactions. J Am Chem Soc 136:17024-35
Zeller, Mary A; Riener, Michelle; Nicewicz, David A (2014) Butyrolactone synthesis via polar radical crossover cycloaddition reactions: diastereoselective syntheses of methylenolactocin and protolichesterinic acid. Org Lett 16:4810-3
Nguyen, Tien M; Manohar, Namita; Nicewicz, David A (2014) anti-Markovnikov hydroamination of alkenes catalyzed by a two-component organic photoredox system: direct access to phenethylamine derivatives. Angew Chem Int Ed Engl 53:6198-201
Riener, Michelle; Nicewicz, David A (2013) Synthesis of cyclobutane lignans via an organic single electron oxidant-electron relay system. Chem Sci 4:
Perkowski, Andrew J; Nicewicz, David A (2013) Direct catalytic anti-Markovnikov addition of carboxylic acids to alkenes. J Am Chem Soc 135:10334-7
Nguyen, Tien M; Nicewicz, David A (2013) Anti-Markovnikov hydroamination of alkenes catalyzed by an organic photoredox system. J Am Chem Soc 135:9588-91
Hamilton, David S; Nicewicz, David A (2012) Direct catalytic anti-markovnikov hydroetherification of alkenols. J Am Chem Soc 134:18577-80