A New Indole Synthesis via Rearrangements of N-Propargylaniline N-Oxides. A One-pot Synthesis of Indole-3-acetonitriles

A new, general method was developed for the synthesis of 3-(substituted-methyl)-indoles from N-propargylanilines. The method involves oxidation of the aniline with m-chloroperbenzoic acid and subsequent treatment with a suitable nucleophilic reagent under mild conditions in a single flask. The possible pathway was indicated to be (a) formation of an N-oxide, (b) [2, 3] and [3, 3] sigmatropic rearrangements of a propargyl group, (c) formation of a 3-methylideneindolenine intermediate, and (d) an attack of a nucleophilic reagent on the methylidene function. The process was quite general and provided a new route for synthesizing 3-(substituted-methyl) indoles-for example, indole-3-acetonitriles, 3-phenylthiomethylindoles, 3-azidomethylindoles and their derivatives.