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Light-driven Enzymatic Decarboxylation
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Continuous Flow Decarboxylative Monofluoroalkylation Enabled by Photoredox Catalysis
Francesco Pasca1, Yuri Gelato1, Michael Andresini1
1Flow Chemistry and Microreactor Technology FLAME-Lab, Department of Pharmacy-Drug Sciences, University of Bari "A. Moro", Bari 70125, Italy.
JACS Au
|February 28, 2025
Summary
This study presents a scalable, mild method for monofluoroalkylation using photoredox catalysis in continuous flow. The approach efficiently introduces fluorinated fragments into diverse molecules, aiding drug discovery.
Area of Science:
- Organic Chemistry
- Photocatalysis
- Flow Chemistry
Background:
- Fluorinated organic compounds are crucial in pharmaceuticals and materials science.
- Developing efficient and mild methods for introducing fluorine is a key challenge in synthetic chemistry.
Purpose of the Study:
- To develop a scalable and mild strategy for monofluoroalkylation of Giese acceptors.
- To utilize visible-light photoredox catalysis in continuous flow for enhanced productivity.
Main Methods:
- Employing a transition-metal-free organic photocatalyst (4CzIPN).
- Utilizing continuous flow technology for improved scalability and safety.
- Accessing monofluoroalkyl radicals from α-monofluorocarboxylic acids.
Main Results:
- Demonstrated a wide functional group tolerance under mild reaction conditions.
- Successfully achieved late-stage monofluoroalkylation of biologically relevant molecules (menthol, amantadine, bepotastine, estrone derivatives).
- Extended the method to a reductive multicomponent radical-polar crossover transformation for increased molecular complexity.
Conclusions:
- The developed method offers a robust and versatile approach for synthesizing monofluoroalkylated compounds.
- This protocol is well-suited for drug discovery programs requiring the incorporation of fluorinated motifs.
- The continuous flow system enhances the practicality and efficiency of photoredox-catalyzed fluorination.
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