Versatile Regioselective Deuteration of Indoles via Transition-Metal-Catalyzed H/D Exchange

The promising application of deuterium-labeled compounds, such as the drug deutetrabenazine, warrants efficient, selective, and direct deuteration of organic entities. Here, we present a highly effective regioselective direct C–H deuteration of indole in D₂O using Cp*Co­(CO)­I₂, [Cp*RhCl₂]₂, or their combination as a catalyst. This transition-metal-catalyzed system made available mono­(C2)-, di­(C2/C7)-, tri­(C2/C3/C7)-, and even C4-deuterated products from diverse indole substrates, equipped with the removable N1-directing group. The selective H/D exchanges on the rest of the sites of the indoles were also realized by shifting the directing group. Furthermore, an example of this approach was demonstrated to acquire deuteromelatonin from the drug melatonin.