Efficient reagents for the synthesis of 5-, 7-, and 5,7-substituted indoles starting from aromatic amines: Scope and limitations

Article abstract of DOI:10.1021/jo952119+

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 bis-annulation 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.