Synthesis of 2-(α-trifluoromethylamino)indoles via stepwise cascade transformation of imidoyl sulfoxonium ylides with ortho-chloromethyl anilines

Abstract

We have developed an efficient one-pot method for the synthesis of 2-(α-trifluoromethylamino)indole scaffolds from CF₃-imidoyl sulfoxonium ylides and ortho-chloromethyl anilines. This transformation exhibits broad functional group tolerance under ambient conditions, giving yields ranging from 49–83% across 23 examples. Mechanistic investigations suggest that the reaction pathway involves an initial cyclization, which is followed by a base-mediated isomerization and rearomatization sequence. This approach offers a novel strategy for introducing α-CF₃ amino groups into heterocycles and presents a valuable alternative for indole synthesis.