Catalysis by ferrous ion in nucleophilic aromatic substitution reactions

Abstract

Efficient catalysis is provided by ferrous chloride in the nucleophilic aromatic substitution reaction of several aryl and heteroaryl halides with a ketone enolate ion as the nucleophile in Me₂SO, to give the aryl or heteroaryl ketones in fair to good yields. The enolate ions from pinacolone, acetophenone, cyclohexanone and pentan-3-one behave successfully. A side-reaction is represented in some cases by the hydrodehalogenation of the substrate ArX, and evidence is provided for the intermediacy of both Ar˙ and Ar^– species. Other significant mechanistic clues acquired include: (i) inhibition by electron and radical scavengers; (ii) entrainment of poor nucleophiles by good ones; (iii) the relative reactivity of two nucleophiles in competition experiments with Phl under Fe²⁺catalysis having the same value as in the experiments under both photostimulation and spontaneous initiation. All these findings are consistent with an S_RN1 mechanism of substitution where ferrous ion, in combination with the nucleophile, plays an important rôle in the initiation step.