Palladium-Catalyzed Methylene β-C-H Fluorination of Native Amides.

ABSTRACT: Selective fluorination of C(sp³)-H bonds is a highly valuable transformation in organic synthesis and drug discovery. However, achieving methylene C-H fluorination of native substrates remains a significant challenge, as it typically requires external directing groups to facilitate catalyst-substrate binding. Herein, we report a ligand-accelerated Pd-catalyzed methylene β-C-H fluorination of native amides using a bidentate neutral amide-pyridone ligand. This ligand design features the enhancement of catalyst-substrate interactions via stabilization of the cationic palladium center and acceleration of methylene C-H activation, enabling the stereo- and site-selective fluorination of native amides under relatively mild conditions. Notably, Pd(II)-catalyzed methylene C-H acti

SUBMITTER: Li YH 

PROVIDER: S-EPMC12334182 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature