Catalyst-free Synthesis of 6-Hydroxy Indoles via the Condensation of Carboxymethyl Cyclohexadienones and Amines

Abstract

An efficient catalyst-free synthesis of 6-hydroxy indoles from carboxymethyl cyclohexadienones and primary amines has been developed. The aza-Michael addition of the in situ formed enamine, generated through the condensation of carboxymethyl unit of the substrates with an external amine, to cyclohexadienone moiety followed by rearomatization reaction to provide such indoles. Anilines, aliphatic amines, α-chiral aliphatic amines, or even ammonia were used as amine counterpart. Some of the cyclohexadienones gave 6-amino indoles instead of 6-hydroxy indoles using the Re₂O₇ catalyst. Various post methodological transformations were performed to explore the synthetic utility of the synthesized hydroxy indoles.