Palladium-Catalyzed Site-Selective Fluorination of Unactivated C(sp³)–H Bonds

The transition-metal-catalyzed direct C–H bond fluorination is an attractive synthetic tool toward the preparation of organofluorines. While many methods exist for the direct sp³ C–H functionalization, site-selective fluorination of unactivated sp³ carbons remains a challenge. Direct, highly site-selective and diastereoselective fluorination of aliphatic amides via a palladium-catalyzed bidentate ligand-directed C–H bond functionalization process on unactivated sp³ carbons is reported. With this approach, a wide variety of β-fluorinated amino acid derivatives and aliphatic amides, important motifs in medicinal and agricultural chemistry, were prepared with palladium acetate as the catalyst and Selectfluor as the fluorine source.