The topological and stereochemical complexity inherent in molecular scaffolds with high sp3 character imparts beneficial physical and biological properties relative to sp2-rich compounds, but also amplifies selectivity and reactivity challenges for their efficient synthesis. Modular strategies for the rapid and selective construction of stereodefined sp3-rich molecules would enable access to a broad range of chemical space and advance a significant frontier in organic synthesis. The Paradine group is interested in leveraging the tools of reaction discovery, transition metal catalysis, and mechanistic investigation to solve important problems in organic synthesis.
Our group will focus on the discovery of selective catalytic methods for the efficient construction of sp3-rich molecules, with a specific focus on C‒C bond formation. A particular priority will be placed on transformations that utilize simple starting materials and lead to a significant increase in molecular complexity. The following are a selection of projects that our group will explore.
Project 1: We will develop a suite of bifunctional reagents for palladium-catalyzed carbofunctionalization reactions to enable the rapid construction of polycyclic aliphatic heterocyclic ring systems.
Project 2: We will explore novel transition metal-catalyzed enantioselective carboxyfunctionalization reactions of π-systems that utilize CO2 as a C1 source of carbon.
Project 3: We are interested in developing a series of tunable manganese(III) carboxylate complexes to catalyze enantioselective radical polycyclization reactions and to discover new radical coupling reactions.
In all cases, we will seek to discover catalytic synthetic methodologies that exert precise control over reaction outcomes (i.e. enantioselectivity, site-selectivity, chemoselectivity, diastereoselectivity), and undertake fundamental studies to understand the factors that contribute to highly selective transformations.
This research provides ample opportunities for applications to catalysis, total synthesis, medicinal chemistry, and other areas. Collaborations with colleagues across disciplines will be sought out to realize the full potential of our group's research. Students in our group will gain expertise in organic synthesis and reaction discovery. In addition, students will learn techniques in physical and mechanistic organic chemistry, spectroscopic characterization of organic compounds, and the synthesis and investigation of transition metal complexes.
- White, M.C.; Paradine, S.M.; Griffin, J.R.; Zhao, J.; Petronico, A.L. “General Catalyst for C–H Functionalization.” U.S. Patent 9,770,711, 2017.
- Paradine, S.M.; Griffin, J.R.; Zhao, J.; Petronico, A.L.; Miller, S.; White, M.C. “A Manganese Catalyst for Highly Reactive yet Selective Intramolecular C(sp3)–H Amination.” Nature Chemistry, 2015, 7, 987-994.
- Paradine, S.M.; White, M.C. “Iron-Catalyzed Intramolecular Allylic C–H Amination.” Journal of the American Chemical Society, 2012, 134, 2036-2039.
- Altermann, S.M.; Richardson, R.D.; Page, T.K.; Schmidt, R.K.; Holland, E.; Mohammed, U.; Paradine, S.M.; French, A.N.; Richter, C.; Bahar, A.M.; Witulski, B.; Wirth, T. “Catalytic Enantioselective α-Oxysulfonylation of Ketones Mediated by Iodoarenes.” European Journal of Organic Chemistry, 2008, 5315-5328.
- Richardson, R.D.; Page, T.K.; Altermann, S.; Paradine, S.M.; French, A.N.; Wirth, T. “Enantioselective α-Oxytosylation of Ketones Catalysed by Iodoarenes.” Synlett, 2007, 538-542.