Copper-Mediated Late-Stage Radical Trifluoromethylation of Pyrazole-Type Scaffolds

Trifluoromethylated pyrazoles and their derivatives are of great interest due to their biological and pharmacological relevance. However, efficient methods for their preparation via late-stage trifluoromethylation strategies remain limited. Herein, we report a practical and efficient method for the direct trifluoromethylation of pyrazoles using in situ generated CF₃ radicals and inexpensive copper-(II) salts as catalysts at room temperature. The method exhibits excellent functional group tolerance. DFT studies support the observed reactivity trends and provide insight into the electronic effects governing CF₃ radical addition. This strategy holds promise for the generation of highly substituted pyrazoles of interest in biomedical and crop-science applications.