Overcoming the ring tension: computational approaches to stereochemical assignments and geometrical insights in small heterocycles
Ezequiel R Luciano1, Milagros Amichetti1,2, Ariel M Sarotti2
1Instituto de Investigaciones en Ingeniería Ambiental, Química y Biotecnología Aplicada (INGEBIO), Facultad de Química e Ingeniería del Rosario, Pontificia Universidad Católica Argentina, Av. Pellegrini 3314, Rosario 2000, Argentina. zanardi@rosario-conicet.gov.ar.
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.
Related Concept Videos
Stereoisomerism of Cyclic Compounds
Thermal Electrocyclic Reactions: Stereochemistry
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
Photochemical Electrocyclic Reactions: Stereochemistry
Selection Rules: Photochemical Activation
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Stability of Substituted Cyclohexanes
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...


