Computational workflow for steric assessment using the electric field-derived size

Abstract Molecular structure plays an important role in the selectivity and performance of catalysts. Understanding the impact of structural differences on catalyst performance via quantitative structure-selectivity relationships is key to developing high-performing catalytic systems. There are several methods that have been introduced to quantify steric contributions, including Tolman cone angles, Charton parameters, and A-values. While these have shown promise in predicting selectivity, they access similar, general steric contributions and are largely empirically derived. Alternatively, Sterimol parameters offer a specific multi-directional measure of steric bulk in the form of three vectors in units of distance. Recently, these parameters revealed strong correlations between structure and selectivity in asymmetric catalysis. Yet, despite their demonstrated performance, Sterimol parameters are commonly derived using van der Waals radii, which approximate molecular size using hard-spheres. This method may not accurately describe highly polarized systems. Recently, a new chemical system size metric based on the electric-field of a molecule was developed, which accesses the occupied space of a molecule. Here, we demonstrate that the electric field-derived Sterimol parameters reveal similar structure-selectivity relationships in asymmetric catalysis as conventional Sterimol parameters. Specifically, we present a computational workflow for calculating Sterimol parameters based on the size of a molecule’s electric field, and validate our method using several asymmetric catalysis reactions.