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

## TL;DR

This study explores how Lewis acids influence Alder-ene reactions using electron density theory, revealing how they lower activation energy and change reaction mechanisms.

## Contribution

The study introduces a new understanding of how Lewis acids modify Alder-ene reaction mechanisms through electronic effects.

## Key findings

- Lewis acids increase the electrophilic character of formaldehyde without altering its electronic structure.
- Lewis acids change the reaction mechanism from a non-concerted one-step to a two-step process.
- Topological analysis shows hydrogen departure lags behind C-C bond formation at transition states.

## Abstract

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 two-stage one-step 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.