Palladium-Catalyzed ortho-Selective C-H Chlorination of Benzamide Derivatives under Anodic Oxidation Conditions.

The palladium-catalyzed ortho-selective chlorination of N-quinolinylbenzamide derivatives with hydrochloric acid was achieved under anodic oxidation conditions. The use of 5,7-dichloro-8-quinolinyl group as directing group was effective for the selective chlorination, and the reaction was applicable to benzamide derivatives bearing various functional groups. Synthesis of vismodegib was also completed using the palladium-catalyzed electrochemical C-H chlorination in two different steps.