Synthesis of Diclofenac and Lumiracoxib

Significance

Arylacetic acids undergo palladium(II)-catalyzed ortho-C-H iodination in the presence of IOAc generated in situ by reaction of PhI(OAc)₂ with iodine. The value of the reaction was illustrated by syntheses of the nonsteroidal anti-inflammatory drugs lumiracoxib and diclo­fenac. A selection of the twenty-three substrates examined shown above illustrates the scope of the reaction. Methoxy-substituted substrates ­react with IOAc non-selectively in the absence of palladium. The reaction must be shielded from light to prevent radical decomposition of acyl ­hypoiodite intermediates.