Insights into the Mechanism, Selectivity, and Substituent Effects in the Diels-Alder Reaction of Azatrienes with Electron-rich Dienophiles: An MEDT Study

TL;DR

This study uses Molecular Electron Density Theory to analyze the mechanism, selectivity, and substituent effects in azatriene Diels-Alder reactions with electron-rich dienophiles, revealing a polar one-step two-stages process.

Contribution

It provides a detailed theoretical insight into the reaction mechanism and selectivity factors of azatriene Diels-Alder reactions, which were previously underexplored.

Findings

Revealed a polar one-step two-stages reaction mechanism.

Established relationships between selectivity and reaction mechanism characteristics.

Demonstrated how substituents influence reaction feasibility through electron density flux.

Abstract

The reactivity and mechanistic intricacies of azatrienes in Diels-Alder reactions have been relatively unexplored despite their intriguing potential applications. In this study, we employ Molecular Electron Density Theory to theoretically investigate the hetero-Diels-Alder reaction involving azatrienes with ethyl vinyl ether and allenyl methyl ether. Analysis of Conceptual Density Functional Theory, energetic profiles, and the topological characteristics is conducted to elucidate the reactions. The revealed mechanism manifests as a polar one-step two-stages process under kinetic control. We establish a clear relationship of between the periselectivity, regioselectivity, and stereoselectivity on one hand and the characteristics of the reactions mechanism on the other hand. The influence of weak interactions on reaction activation barriers and bonding evolution are discussed in detail. We demonstrate that substituents enhancing the reverse electron density flux facilitate the feasibility of the reactions. The results lay ground for a meticulous control of the reaction of azatriene in similar synthetic scenarios.