Catalysis by ferrous ion in nucleophilic aromatic substitution reactions

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 SRN1 mechanism of substitution where ferrous ion, in combination with the nucleophile, plays an important rôle in the initiation step.