Access to SCF3-Substituted Indolizines via a Photocatalytic Late-Stage Functionalization Protocol.
Kevin Klaus Stefanoni1, René Wilhelm1
1Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstr. 6, 38678 Clausthal-Zellerfeld, Germany.
Organic Letters
|July 21, 2025
Summary
A new photocatalytic method enables direct indolizine functionalization using N-((trifluoromethyl)thio)saccharin. This scalable approach yields desired products and shows potential for synthesizing biologically relevant molecules.
Area of Science:
- Organic Chemistry
- Photocatalysis
- Medicinal Chemistry
Background:
- Indolizine derivatives are important scaffolds in medicinal chemistry.
- Developing efficient methods for direct functionalization of heterocycles is crucial.
- Existing methods for trifluoromethylthiolation can be harsh or lack selectivity.
Purpose of the Study:
- To develop a mild, scalable, and chemoselective photocatalytic method for direct indolizine functionalization.
- To introduce the trifluoromethylthio (SCF3) group onto the indolizine core.
- To demonstrate the utility of this method in synthesizing biologically relevant molecules.
Main Methods:
- Utilized a photoredox catalyst for direct C-H functionalization of indolizines.
- Employed N-((trifluoromethyl)thio)saccharin as the trifluoromethylthiolating reagent.
- Optimized reaction conditions for mildness, scalability, and chemoselectivity.
Main Results:
- Achieved high yields of directly functionalized indolizines.
- Demonstrated excellent chemoselectivity, tolerating various functional groups.
- Successfully synthesized a 3-SCF3 analogue of a histamine H3 receptor antagonist with high yield.
Conclusions:
- The developed photocatalytic method is mild, scalable, and highly chemoselective.
- The employed photoredox catalyst is a cost-effective alternative.
- This strategy holds significant potential for the synthesis of novel drug candidates and biologically active compounds.
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