Electrophilic Intermediates in the Nef and Meyer Reactions: A Computational Study

The generation, interconversion, and reactivity of electrophilic species generated upon activation of nitroalkanes with protic acids (the Nef and Meyer reactions) were investigated by quantum-chemical calculations. <i>N</i>,<i>N</i>-Bis(hydroxy)iminium (R₂C═N⁺(OH)₂) and <i>N</i>-oxoiminium (R₂C═N⁺═O) cations were shown to be produced independently from <i>aci</i>-nitroalkanes, while <i>N</i>-hydroxynitrilium cations (RC≡N⁺-OH) were formed via nearly barrierless C-H bond cleavage in <i>N</i>-oxoiminium cations. The <i>N</i>-oxoiminium and <i>N</i>-hydroxynitrilium cations whose formation is favored under highly acidic anhydrous conditions are strong electrophiles capable of reacting even with nonactivated arenes under ambient conditions. The <i>N</i>-oxoiminium cations R₂C═N⁺═O are highly unusual ambident species containing three contiguous electrophilic centers (C, N, and O atoms). Nucleophilic addition at the oxygen atom is less preferred than the C- and N-attack yet possible in an intramolecular variant. These computational results shed light on some key aspects of the mechanisms of the Nef and Meyer reactions and predict the possibility of numerous interrupted versions of these reactions.