Amide-Ligand-Promoted Silver-Catalyzed C-H Fluorination via Radical/Polar Crossover

We describe an efficient method for benzylic C-H fluorination via sequential hydrogen-atom transfer (HAT) and oxidative radical-polar crossover utilizing the Ag(I)/Selectfluor system. Amide ligands, such as benzamide and sulfonamide, substantially facilitate the processes leading to a carbocation intermediate, which subsequently reacts with nucleophilic fluorinating reagent to form a C-F bond. This protocol is applicable to the fluorination of all 1 degrees, 2 degrees, and 3 degrees C-H bonds as well as to late-stage C-H fluorination of bioactive molecules.

Automated summary

We describe an efficient method for benzylic C-H fluorination via sequential hydrogen-atom transfer (HAT) and oxidative radical-polar crossover utilizing the Ag(I)/Selectfluor system. Amide ligands, such as benzamide and sulfonamide, substantially facilitate the processes leading to a carbocation intermediate, which subsequently reacts with nucleophilic fluorinating reagent to form a C-F bond. This protocol is applicable to the fluorination of all 1 degrees, 2 degrees, and 3 degrees C-H bonds as well as to late-stage C-H fluorination of bioactive molecules.