Overcoming the ring tension: computational approaches to stereochemical assignments and geometrical insights in small heterocycles

Abstract

In this study, we evaluate the performance of the DP4+ and MM-DP4+ methods on molecules featuring small heterocyclic rings. A dataset of 71 molecules containing three- and four-membered heterocycles, known for their stereochemical assignment challenges, was analyzed. We compared molecular geometries optimized at different computational levels, including MMFF and B3LYP/6-31G*, to assess deviations in key geometric parameters relative to the heterocycle structures. Furthermore, the geometric properties of these molecules were investigated using various force fields to evaluate their differences. Our aim was to assess the reliability of B3LYP/6-31G* in comparison with more accurate methods and to elucidate how different force fields influence in geometric precision.