Mild C─F Activation of Azido(per)Fluoroalkanes
Olena Shaitanova1,2, María Martínez Mallo1,3, Sergii Suikov1
1Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czechia.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|July 10, 2026
Summary
Researchers developed a new method for activating C(sp3)-F bonds in fluorinated azidoalkanes using electrophilic azides. This approach enables mild, high-yield synthesis of diverse sulfur-containing compounds without metal catalysts.
Area of Science:
- Organic Chemistry
- Fluorine Chemistry
- Catalysis
Background:
- Carbon-fluorine (C-F) bonds are prevalent in pharmaceuticals and materials but challenging to activate selectively.
- Existing C-F activation methods often require harsh conditions, expensive catalysts, or lack functional group tolerance.
Purpose of the Study:
- To develop a novel, mild, and selective method for activating C(sp3)-F bonds in fluorinated azidoalkanes.
- To synthesize new nitrogen- and sulfur-containing organic scaffolds from readily available fluorinated azides.
Main Methods:
- Utilizing electrophilic azide groups to promote fluoride elimination and subsequent nucleophilic addition.
- Employing mild reaction conditions with inexpensive reagents, avoiding metal catalysts and external energy input.
- Conducting mechanistic investigations using spectroscopy, X-ray crystallography, and ab initio calculations.
Main Results:
- Achieved rapid, high-yield transformations of (per)fluoroalkyl azides into diverse sulfur-containing azides, imines, and triazoles.
- Demonstrated broad functional group tolerance, including compatibility with thiol-sensitive motifs.
- Elucidated the reaction mechanism involving key azide intermediates and a denitrogenation pathway.
Conclusions:
- The developed method offers a practical and scalable route for C-F bond activation in fluorinated azidoalkanes.
- This approach provides access to valuable nitrogen- and sulfur-functionalized compounds under mild conditions.
- Advances the field of C-F activation chemistry with a versatile and efficient transformation.
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