Understanding [3+2] cycloaddition reactions of difluoroallene to nitrone and diazoalkanes from the molecular electron density theory perspective

Abstract

A detailed theoretical study at the MPWB1K/6-311G(d,p) computational level for the [3+2] cycloaddition (32CA) reactions of 1,1-difluoroallene (DFA) with Z-C-phenyl-N-methyl nitrone (NI), diazomethane (DM) and dimethyl diazomethane (MDM) in the light of molecular electron density theory (MEDT) is herein reported. These 32CA reactions are energetically aligned towards the addition along the non-fluorinated double bond of DFA in each case, in complete agreement with the experiments. The 32CA reactions involving the nitrone and DM were regiospecific, while that of MDM was devoid of any regiochemical control. This could be revealed from the analysis of the corresponding energy profiles for these exergonic kinetically controlled 32CA reactions, following a one-step mechanism via high asynchronous single bond formation processes, also implied by the topological analysis of the electron localization function (ELF) along the more favorable reaction paths. Finally, analysis of the quantum theory of atoms-in-molecules (QTAIM) parameters indicates the absence of any covalent interaction between the two pairs of interacting centers at any transition state structure, which is visualized in the non-covalent interaction (NCI) isosurfaces, in agreement with the ELF analyses.