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

## TL;DR

A new copper-catalyzed method allows efficient and selective trifluoromethylation of pyrazole compounds at room temperature.

## Contribution

A practical late-stage radical trifluoromethylation method using copper catalysts and CF3 radicals for pyrazole scaffolds.

## Key findings

- The method shows excellent functional group tolerance for pyrazole trifluoromethylation.
- DFT studies explain the electronic effects influencing CF3 radical addition.
- The strategy enables the synthesis of highly substituted pyrazoles relevant to biomedical and agricultural applications.

## Abstract

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.