Research

Research in our group spans the realm of synthetic organic chemistry, medicinal chemistry, natural products chemistry and methodology development.  Our research is primarily motivated by the interest in developing new synthetic methodologies that can be applied toward the construction of complex natural products and pharmaceutically-interesting compounds. Topic areas include:

1. Synthetic Methods
2. Complex Synthesis of Natural Products and their Derivatives
3. Carbohydrate Upcycling
4. Catalyst Design
5. Medicinal Chemistry and Chemical Biology
6. Non-biological Applications of Small Molecules
7. Environmental and Atmospheric Chemistry
8. Degradable polymer cross-linking for improved paper technology
   

1. Synthetic Methods

Our group is interested in the design of efficient methodologies to accomplish the formation of carbon-carbon and carbon-heteroatom bonds with the intent to apply the methodology toward the synthesis of complex natural and unnatural targets.

Representative publications:

• Rh(II)-catalyzed Intermolecular Benzylic C(sp³)-H Alkylation of Methyl-substituted Arenes by N-Aryl-α-diazo-β-amidoesters. ChemCatChem 2022, e202101977.

• Catalyst-controlled Chemodivergent Reactions of 2-Pyrrolyl-a-diazo-b-ketoesters and Enol Ethers: Synthesis of 1,2-Dihydrofuran Acetals and Highly Substituted Indoles. Journal of Organic Chemistry 2021, 86, 10088-10104.
• Efforts towards Rh(II)-catalyzed N-alkoxyazomethine ylide generation: Disparate reactivities of O-tethered a-diazo keto and -b-ketoester oximes. Tetrahedron 2020, 76: 131501.

2. Complex synthesis of Natural Products and their Derivatives

Approaches to natural products (NPs) not only inspire the development of new synthetic strategies, but often unveil unexpected and often interesting reactivity. Targets are chosen for their interesting biological activity along with their sheer complexity. We are interested in exploring both modular and convergent approaches to complex targets that enable facile derivatization for the development of combinatorial libraries. We employ both top-down and bottom-up approaches toward NPs.

Representative publications:

• Intramolecular, Interrupted Homo-Nazarov Cascade Biscyclizations to Angular (Hetero)Aryl-fused Polycycles. Chemistry- A European Journal 2022, Accepted Article.
• Diastereoselective Synthesis of (+/-)-Deethyleburnamonine Using a Catalytic Cyclopropane Ring-Opening/Friedel-Crafts Alkylation Strategy. Heterocycles 2012, 84, 1363.

3. Carbohydrate Upcycling (collaboration with Jones Lab, ChBE)

Carbohydrates, one of the most abundant and common forms of biomass, have been the center of much of the research focused on finding new and efficient renewable feedstock upgrading technologies. To date, the valorization of cellulose has been focused on its conversion to low-cost platform chemicals like levulinic acid, substituted furfurals, sugar alcohols, lactic acid, phenols, and succinic acid. Despite these important examples, carbohydrate upgrading technologies have remained limited. A pressing need exists for the identification and development of technologies that offer new platform chemicals that can be utilized on a production scale. The France lab is exploring chemo-catalytic approaches to: (1) the direct cellulose valorization to form polyhydroxyalkyl and/or C-glycosyl furans through “endwise peeling”; (2) exploitation of furan-containing products as versatile building blocks for further organic synthesis, and (3) the at-scale conversion of furan-containing products to branched hydrocarbon fuel additives.

Representative publications:

• Selective Conversion of Malononitrile and Unprotected Carbohydrates to Bicyclic Polyhydroxalkyl Dihydrofurans using Magnesium Oxide as a Recyclable Catalyst. ACS Sustainable Chemistry & Engineering 2022, 10, 5966–5975.
• Modulation and Tuning of UiO-66 for Lewis acid Catalyzed Biomass Conversion: Catalysis of Unprotected Aldose Sugars to Polyhydroxyalkyl and C-Glycosyl Furans. ACS Sustainable Chemistry & Engineering 2021, 9, 11581-11595.
• Conversion of Unprotected Aldose Sugars to Polyhydroxyalkyl and C-Glycosyl Furans via Zirconium Catalysis. Journal of Organic Chemistry 2020, 85, 15337-15346.

4. Catalyst Design

We are interested in the design, synthesis, and evaluation of homogeneous and heterogeneous catalysts that enable organic transformations. Chiral organocatalysts, transition metal and main group metal catalysts are particular areas of focus within the group.

Representative publications:

• Chiral Disulfonimides: A Versatile Template for Asymmetric Catalysis. Organic and Biomolecular Chemistry 2020, 18, 7485-7513.
• A Predictive Model for the [Rh₂(esp)₂]-catalyzed Intermolecular C(sp³)-H Insertion of b-Carbonyl Ester Carbenes: Interplay Between Theory and Experiment. ACS Catalysis 2019, 9, 4526-4538.

5. Medicinal Chemistry and Chemical Biology

Medicinal or pharmaceutical chemistry lies at the intersection of chemistry and pharmacy. Our group is interested in the design, synthesis and development of pharmaceutical drugs, or other chemical entities suitable for therapeutic use. We are further interested in the study of their biological properties and their quantitative structure-activity relationships (QSAR). Given that medicinal chemistry is a highly interdisciplinary science, we aim to establish several collaborations with biologists, biochemists, and computational chemists to facilitate the design and development process. In particular, we aim to develop therapeutics toward the treatment of various forms of cancer, HIV, diabetes, and neurological disorders, such as Alzheimer’s and Parkinson’s disease.

Representative publications:

• Synthetic methodology-enabled discovery of a tunable indole template with selective COX-1 inhibition and anti-cancer activities. Bioorganic Medicinal Chemistry 2022, 57, 116633.
• Ligands for glaucoma-associated myocilin discovered by a generic binding assay. ACS Chemical Biology 2014, 9, 517-25. (collaboration with Lieberman Lab)

6. Non-biological Applications of Small Molecules

We are interested in the synthesis and application of small molecules as useful materials, fuels, chemical additives, and forensic standards.

Representative publications:

• Completion of the Set: Synthesis of the (6,X’)-Flubromazepam Positional Isomers as Standards for Forensic Analysis.
• Synthesis of Flubromazepam Positional Isomers for Forensic Analysis. Journal of Organic Chemistry 2019, 84, 10280-10291.
• Novel Heat Transfer Fluids for Direct Immersion Phase Change Cooling of Electronic Systems. International Journal of Heat and Mass Transfer 2012, 55, 3379-3385.

7. Environmental and Atmospheric Chemistry (collaboration with Ng Lab)

We are interested in the synthesis of volatile organic compounds (VOCs) that can be used to probe environmental and atmospheric phenomena.

Representative publications:

• Synthesis and hydrolysis of atmospherically relevant monoterpene-derived organic nitrates. Environmental Science & Technology 2021, 55, 14595-14606.
• Theodora Nah,* Lu Xu, Kymberlee A. Osborne-Benthaus, S. Meghan White,^@ Stefan France, Nga Lee Ng.* Mixing Order of Sulfate Aerosols and Isoprene Epoxydiols Affect Secondary Organic Aerosol Formation in Chamber Experiments. Atmospheric Environment 2019, 217, 15, 116953

8. Degradable polymer cross-linking for improved paper technology (collaboration with the Brettmann Lab, ChBE).

To improve recyclability and provide more sustainable products, paper products such as packaging and towels, which are typically formulated to maintain high strength even in the presence of water, must be able to degrade in a short time after use. The France lab is developing new wet strength additive chemistries that degrade in response to light/UV or moisture, while still providing sufficient strength and durability. Three approaches are being explored: 1) polymers containing UV- or NIR-degradable linkages, 2) polymers based on poly(beta amino esters) that undergo hydrolysis on a timescale that can be tuned through hydrophobicity and 3) time-release particles that contain an additional chemical compound that triggers degradation. The France lab is studying the impact of polymer structure on the degradation profile and mechanical properties of the resulting paper, while also considering industrially-relevant challenges such as cost, safety and scalability.