Green oxidation of indoles using halide catalysis

Oxidation of indoles is a fundamental organic transformation to deliver a variety of synthetically and pharmaceutically valuable nitrogen-containing compounds. Prior methods require the use of either organic oxidants ( meta -chloroperoxybenzoic acid, N-bromosuccinimide, t -BuOCl) or stoichiometric toxic transition metals [Pb(OAc) 4 , OsO 4 , CrO 3 ], which produced oxidant-derived by-products that are harmful to human health, pollute the environment and entail immediate purification. A general catalysis protocol using safer oxidants (H 2 O 2 , oxone, O 2 ) is highly desirable. Herein, we report a unified, efficient halide catalysis for three oxidation reactions of indoles using oxone as the terminal oxidant, namely oxidative rearrangement of tetrahydro-β-carbolines, indole oxidation to 2-oxindoles, and Witkop oxidation. This halide catalysis protocol represents a general, green oxidation method and is expected to be used widely due to several advantageous aspects including waste prevention, less hazardous chemical synthesis, and sustainable halide catalysis. Indole oxidation represents a fundamental organic transformation delivering valuable nitrogen compounds. Here, the authors report a general halide catalysis protocol applied to three classes of oxidation reactions of indoles with oxone as a sustainable terminal oxidant.