para-Selective Radical Trifluoromethylation of Benzamide Derivatives via Iminium Intermediates

The direct C-H trifluoromethylation of arenes via a radical pathway has attracted considerable attention recently. However, a major challenge of C-H trifluoromethylation is the lack of site-selectivity on the phenyl ring especially para-selectivity. Herein we show a new strategy for para-selective C-H trifluoromethylation of benzamide derivatives using iminium activation. The reaction undergoes a radical-type nucleophilic substitution instead of a radical-type electrophilic substitution owing to iminium activation as a result of lowering the LUMO (lowest unoccupied molecular orbital). A wide range of substrates are compatible with this method giving almost exclusive para-trifluoromethylated products.

Automated summary

The direct C-H trifluoromethylation of arenes via a radical pathway has recently gained considerable attention. However, a major challenge in C-H trifluoromethylation is the lack of site-selectivity on the phenyl ring, especially para-selectivity. Here, we demonstrate a new strategy for para-selective C-H trifluoromethylation of benzamide derivatives using iminium activation.