Synthesis of Indoles via Iron-Catalyzed Heteroannulative Oxidative Coupling

Significance

Reported is the synthesis of indoles 2 via an intramolecular iron(III)-catalyzed oxidative coupling of 3-(arylamino)butenoates 1. Optimization of the reaction conditions indicated that the preformed mixed copper salt Cu(OAc)₂˙CuCl₂ was the best stoichiometric oxidant. The reaction displays good functional group tolerance, although yields are often moderate. In general, substrates bearing para-EDG substituents gave better yields than those bearing the same ortho-EDG substituents. In contrast, EWGs were preferred at the ortho-position. Notably, this cyclization is amenable to the construction of indoles bearing halogens (Cl, Br, I) at several different positions on the aromatic ring giving products suitable for further functionalization by traditional coupling ­reactions.