One-Pot Synthesis of Azaindoles and Indoles

Significance

An efficient, Pd-catalyzed route to indoles and azaindoles via intermediate, non-isolable Sonogashira coupling products, is described. Starting with the readily available and inexpensive 2-chloroaniline and 3-amino-2-chloropyridine derivatives, obtained by reductive alkylation of the corresponding amino compounds with aldehydes and ketones, a palladium-catalyzed, copper-free Sonogashira coupling with X-Phos or dppb as ligands, followed by an in situ base-mediated indolization, was developed. The scope of this method is shown by a synthesis of 10 azaindoles with good to excellent yields (83-91%) and 4 indoles in moderate to good yields (50-84%) with relatively broad R² and less general R¹ and R³ substitution patterns.