Understanding Organic Chemistry Using Energy Decomposition Methods

Abstract

The main challenge in computational organic chemistry is translating computational results from methods such as Density Functional Theory, that is, electron density, into chemical understanding and predictive models. Energy Decomposition Analysis (EDA) has emerged as a crucial method for understanding chemical interactions, offering interpretable insights and facilitating the creation of straightforward models. However, a challenge in the applications of EDA is the selection of geometries to compare. For instance, to analyze the origin of the Bürgi-Dunitz angle, the angle of attack of a nucleophile on a carbonyl, one must select different attack angles for comparison, such as the optimal 111° angle and a theoretical 90° angle. This comparison does not provide a full explanation of the origin; rather, it explains why one angle is favored over another. To address this issue, we have recently introduced 2D-EDA for analyzing energy surfaces [1]. This method allows for the analysis of a broad range of angles and distances simultaneously, enabling qualitative and quantitative insights of the whole energy surface. This method was subsequently applied to the origin of linearity in halogen bonds (Figure 1) [2], and is currently used to analyze asynchronicity in Diels–Alder cycloadditions.