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, OsO4, CrO3], 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 (H2O2, oxone, O2) 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.Published versionThis research was financially supported by Research Grant Council of Hong Kong (16311716, 16303617, 16304618) and National Natural Science Foundation of China (21772167). Dr. J.X. also acknowledged the Doctor Start-up Fund ([2018]28) and the Guizhou Province First-Class Disciplines Project (Yiliu Xueke Jianshe Xiangmu-GNYL [2017]008) from Guizhou University of Traditional Chinese Medicine (China)