Radical C-H Trifluoromethoxylation of (Hetero)arenes with Bis(trifluoromethyl)peroxide

Trifluoromethoxylated (hetero)arenes are of great interest for several disciplines, especially in agro- and medicinal chemistry. Radical C-H trifluoromethoxylation of (hetero)arenes represents an attractive approach to prepare such compounds, but the high cost and low atom economy of existing (OCF3)-O-. radical sources make them unsuitable for the large-scale synthesis of trifluoromethoxylated building blocks. Herein, we introduce bis(trifluoromethyl)peroxide (BTMP, CF3OOCF3) as a practical and efficient trifluoromethoxylating reagent that is easily accessible from inexpensive bulk chemicals. Using either visible light photoredox or TEMPO catalysis, trifluoromethoxylated arenes could be prepared in good yields under mild conditions directly from unactivated aromatics. Moreover, TEMPO catalysis allowed for the one-step synthesis of valuable pyridine derivatives, which have been previously prepared via multi-step approaches.

Automated summary

The introduction of bis(trifluoromethyl)peroxide as a practical trifluoromethoxylating reagent opens up a new and efficient method for preparing trifluoromethoxylated arenes. This reagent, easily accessible from inexpensive bulk chemicals, allows for the preparation of trifluoromethoxylated arenes in good yields under mild conditions directly from unactivated aromatics using visible light photoredox or TEMPO catalysis. Additionally, TEMPO catalysis enables the one-step synthesis of valuable pyridine derivatives, simplifying the synthetic process.