Regioselectivity of the coupling between radicals and ambident nucleophiles. A theoretical study

We here report a theoretical study on the reaction of the anions of phenol, 2-naphthol, the pyrimidine bases (uracil, thymine, cytosine), pyrrole, imidazole and benzimidazole with phenyl and 4-nitrobenzyl radicals with the aim of interpreting the factors that control the regiochemical outcome of these reactions; their main features being C-C bond formation with phenyl radicals and C-heteroatom bond formation with 4-nitrobenzyl radicals. The preferred coupling positions were investigated by evaluation of the frontier molecular orbital theory (FMO) indexes and the potential energy surfaces both at the AM1 and DFT/B3LYP levels. Within the latter methodology, the solvent effect was considered under a continuum model. While FMO predicts the experimental regioselectivity of phenyl radicals with good accuracy, it fails in the nitrobenzyl case. On the other hand, studies of transition state stabilities provide a good prediction of the observed regioselectivity for both types of radicals, mainly when the solvent is taken into account.