Computational exploration of the reactionmechanism of the Cu + -catalysed synthesis of indoles from N-aryl enaminones

Abstract

We have studied the role of Cu+ -phenantroline as a catalyst in the cyclization ofN-aryl-enaminones using density-functional theory computations. The catalyst was found to bind the substrate upon deprotonation of its eneaminone, and to dramatically increase the acidity of the carbon adjacent to the ketone functionality. The deprotonation of this carbon atom yields a carbanion which attacks the aryl moiety, thereby closing the heterocycle in the rate-determining step. This C–C bond forming reaction was found to proceed much more rapidly when preceded by re-protonation of the substrate N-atom (which had lost H+ in the initial step).