Unveiling the Role of the Lewis Acids in the Acceleration of Alder-Ene Reactions: A Molecular Electron Density Theory Study

The electronic effects of Lewis acids (LAs) in reducing the activation energies of Alder-ene (AE) reactions have been studied within the Molecular Electron Density Theory (MEDT). To this end, the AE reactions of 2-methylbutadiene (2MBD) with formaldehyde (CHO) in the presence of three LAs with increasing acidic character, BH₃, BF₃, and AlCl₃, have been studied. Topological analysis of the electron density and the evaluation of the DFT-based reactivity indices indicate that LAs do not modify the electronic structure of the carbonyl group but markedly increase the electrophilic character of CHO. LAs not only strongly accelerate the AE reactions, but also modify the molecular mechanisms, changing them from a non-concerted <i>two-stage one-step</i> mechanism to a two-step one. Topological analyses of the electron density at the transition state structures (TSs) indicate that while the formation of the new C-C single bond has begun, the departure of the hydrogen has not yet started. A Relative Interacting Atomic Energy (RIAE) analysis of the activation energies allows the establishment of the electronic effects of LAs on the AE reactions. LAs increase the global electron density transfer (GEDT) occurring in polar AE reactions; this phenomenon markedly stabilizes the CHO framework at the TSs, decreasing the RIAE relative energies.