Protodefluorinated Selectfluor® Aggregatively Activates Selectfluor® for Efficient Radical C(sp3)-H Fluorination
Shahboz Yakubov1, Bastian Dauth1, Willibald J Stockerl1
1Institute of Organic Chemistry, University of Regensburg, Universitätsstr. 31, 93053, Regensburg, Germany.
Chemsuschem
|June 14, 2024
Summary
Researchers discovered that H-TEDA(BF4)2, a waste product from Selectfluor® fluorination, significantly enhances reaction rates and yields. This waste upcycling improves efficiency in radical C(sp3)-H fluorination for medicinal chemistry and materials science.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Materials Science
Background:
- Efficient fluorination is crucial for synthesizing complex molecules and advanced materials.
- Selectfluor® is a widely used reagent for radical C(sp3)-H fluorination under mild conditions.
- The byproduct H-TEDA(BF4)2 from Selectfluor® reactions is typically discarded as waste.
Purpose of the Study:
- To investigate the potential of using the Selectfluor® byproduct, H-TEDA(BF4)2, as a promoter in radical fluorination reactions.
- To enhance the efficiency and yield of C(sp3)-H fluorination processes.
- To elucidate the mechanistic role of H-TEDA(BF4)2 in these transformations.
Main Methods:
- Radical C(sp3)-H fluorination reactions were conducted using Selectfluor®.
- H-TEDA(BF4)2 was added as a promoter in varying reaction conditions (photochemical, photocatalytic, thermal).
- Mechanistic studies, including investigations into aggregation effects, were performed to understand the promotion.
Main Results:
- The addition of H-TEDA(BF4)2 significantly increased reaction rates and overall yields of fluorinated products (average ~3.3x higher).
- The promotive effect was observed across photochemical, photocatalytic, and thermal radical fluorination reactions.
- Mechanistic studies revealed the importance of aggregation changes in Selectfluor® and H-TEDA(BF4)2 for reaction efficiency.
Conclusions:
- H-TEDA(BF4)2, previously considered waste, can be effectively upcycled as a promoter to enhance radical C(sp3)-H fluorination.
- This discovery offers a more sustainable and efficient approach to late-stage fluorination.
- Understanding aggregation phenomena provides new insights into the mechanism of radical fluorination reactions.
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