Iterative double cyclization reaction by SRN1 mechanism. A theoretical interpretation of the regiochemical outcome of diazaheterocycles

Abstract

In this report, we present a synthetic and mechanistic study of novel iterative double cyclization intramolecular S_RN1 reactions from diamides bearing two aryl iodide moieties. This cyclization affords aromatic diazaheterocyclic compounds in good yields. Two synthetic strategies were employed for their preparation: intramolecular S_RN1 and Homolytic Aromatic Substitution. The mechanism is non-trivial and we propose that radicals are intermediates. The regiochemistry was studied using computational calculations, employing the DFT method and the B3LYP functional. It was found that the distribution of products depends on the cyclization activation energies, proportion of neutral conformers, and the type of the electron transfer reaction.