Efficient Reagents for the Synthesis of 5-, 7-, and 5,7-Substituted Indoles Starting from Aromatic Amines: Scope and Limitations

Upon reaction with IPy2BF4, 4-substituted anilines give regioselectively the corresponding o-iodoanilines in nearly quantitative yield, in a process that can be carried out on a multigram scale. Palladium-catalyzed coupling of the resulting 2-iodoanilines with (trimethylsilyl)acetylene (TMSA), followed by efficient CuI-mediated nitrogen cyclization onto alkynes with concurrent elimination of the TMS substituent, allows a straightforward elaboration of 5-mono- and 5,7-disubstituted indoles from aromatic amines. This new approach to the aforementioned indoles does not requires protective groups on nitrogen at any step and can be adapted for preparing related 7-monosubstituted indoles. Moreover, examples iterating the process are given, allowing bisannulation and sequential double annulation and resulting in synthesis of benzodipyrroles. Additionally, suitable conditions for iodination of some of the target indoles with IPy2BF4 are discussed.