The solvent effect on two competing reaction mechanisms involving hypervalent iodine reagents (λ(3)-iodanes): facing the limit of the stationary quantum chemical approach.

Trifluoromethylation of acetonitrile with 3,3-dimethyl-1-(trifluoromethyl)-1λ(3),2- benziodoxol is assumed to occur via reductive elimination (RE) of the electrophilic CF3-ligand and MeCN bound to the hypervalent iodine. Computations in gas phase showed that the reaction might also occur via an SN2 mechanism. There is a substantial solvent effect present for both reaction mechanisms, and their energies of activation are very sensitive toward the solvent model used (implicit, microsolvation, and cluster-continuum). With polarizable continuum model-based methods, the SN2 mechanism becomes less favorable. Applying the cluster-continuum model, using a shell of solvent molecules derived from ab initio molecular dynamics (AIMD) simulations, the gap between the two activation barriers ( ΔΔG‡) is lowered to a few kcal mol(-1) and also shows that the activation entropies (ΔS‡) and volumes (ΔV‡) for the two mechanisms differ substantially. A quantitative assessment of ΔΔG‡ will therefore only be possible using AIMD. A natural bond orbital-analysis gives further insight into the activation of the CF3-reagent by protonation.