Palladium-catalyzed directed synthesis of -deuterated phenylacetic acid and analogues.

The synthesis of deuterium-labeled organic compounds is of increased interest, especially after the approval of deutetrabenazine by the Food and Drug Administration in 2014. The selective incorporation of deuterium in the place of hydrogen not only represents uniqueness in terms of a novel chemical class, but it also can improve the pharmacokinetic profiles of drug molecules while retaining potency and other parameters; thus, hydrogen-deuterium (H/D) exchange methods have been proven to be powerful additions in different areas of chemical science. In that regard, metal-catalyzed deuterium labeling via C-H activation mediated by a unique inbuilt directing group (DG) can play a significant role in the synthesis of novel deuterated chemical entities.