# Intramolecular Versus Intermolecular Diels–Alder Reactions: Insights from Molecular Electron Density Theory

## TL;DR

This study compares intramolecular and intermolecular Diels–Alder reactions using electron density theory, finding they are electronically and energetically similar, with speed differences due to entropy.

## Contribution

The study reveals that intramolecular and intermolecular Diels–Alder reactions are electronically and energetically similar, differing mainly in activation entropy.

## Key findings

- Substitution does not alter the electronic structure or reactivity of reagents in intramolecular versus intermolecular processes.
- Intramolecular reactions are 10⁴ times faster due to lower unfavorable activation entropy, not electronic differences.
- Electrophilic frameworks are stabilized, reducing activation energies in polar intramolecular reactions.

## Abstract

The intramolecular Diels–Alder (IMDA) reactions of four substituted deca-1,3,9-trienes and one N-methyleneocta-5,7-dien-1-aminium with different electrophilic/nucleophilic activations have been studied within the Molecular Electron Density Theory (MEDT) and compared to their intermolecular processes. The topological analysis of the electron density and DFT-based reactivity indices reveal that substitution does not modify neither the electronic structure nor the reactivity of the reagents relative to those involved in the intermolecular processes. The analysis of the relative energies establishes that the accelerations found in the polar IMDA reactions follow the same trend as those found in the intermolecular processes. The geometries and the electronic structures of the five transition state structures involved in the IMDA reactions are highly similar to those found in the intermolecular processes. A relative interacting atomic energy (RIAE) analysis of Diels–Alder and IMDA reactions allows for the establishment of the substituent effects on the activation energies. Although the nucleophilic frameworks are destabilized, the electrophilic frameworks are further stabilized, resulting in a reduction in the activation energies. The present MEDT study demonstrates the remarkable electronic and energetic similarity between the intermolecular and intramolecular Diels–Alder reactions. Only the lower, unfavorable activation entropy associated with the latter renders it 104 times faster than the former.