Synthesis of 2,3-Disubstituted Indoles by Iron(II)-Catalyzed Aromatic C-H Amination

Significance

Reported is a general synthesis of 2,3-disubstituted indoles 2 via a ring opening of aryl 2H-azirines 1 catalyzed by FeCl₂. Based on previous results (K. Isomura, K. Uto, H. Taniguchi J. Chem. Soc., Chem. Commun. 1977, 664; S. Chiba, G. Hattoti, K. Narasaka Chem. Lett. 2007, 36, 52), the 2H-azirine 1 is converted into indole 2 via a proposed vinyl nitrene intermediate. After screening several iron sources, the best results were obtained using FeCl₂. Amides, aryl (substituted by EWGs and EDGs) halides, OTBS and CF₃ substituents are tolerated in the reaction. Moreover, the annulation tolerates various aryl and alkyl C2- and C3-substituents in the 2H-azirine 1. The apparent single limitation is the requirement of a R^¹ substituent. Finally, a plausible mechanism involving an iron nitrene complex was proposed.