Halogenation of Indoles with Copper(II) Halides: Selective Synthesis of 2-Halo-, 3-Halo-, and 2,3-Dibromoindoles

A simple and selective protocol for the halogenation of indoles with copper(II) bromide or chloride to synthesize 2-halo-, 3-halo-, and 2,3-dibromoindoles was developed. It was found that both base and water could be used as switches for the selectivity of the halogenation reactions. In the presence of copper(II) halide and sodium hydroxide, 3-haloindoles were obtained as the major products, whereas the selectivity was shifted toward 2,3-dihaloindoles when water was added instead of sodium hydroxide. Moreover, 2-halogenations of 3-substituted indoles were also performed successfully in moderate to good yields under the standard conditions.