London Dispersion: From Molecular Balances to Organic Synthesis

Abstract

London dispersion interactions are a ubiquitous attractive component of van der Waals interactions in chemistry. They represent a key driving force for molecular aggregation and can significantly influence the structure, stability, and selectivity of chemical systems. The aim of this work is to demonstrate how London dispersion interactions can be enhanced through the targeted combination of molecular fragments, what influence the solvent exerts on these interactions, and to what extent established chemical reactions already exploit or insufficiently account for these forces. Furthermore, it is investigated how considering dispersion interactions can extend our understanding of reaction mechanisms and, in some cases, even redefine them. In the first research article, the targeted enhancement and quantification of London dispersion interactions was the central focus. Diphenylthioureas with dispersion energy donors in the meta-position were investigated, which enabled stabilization of the previously little-studied syn–syn conformer. Using low-temperature NMR spectroscopy and quantum chemical methods, the contributions of different substituents to conformational stabilization and the strength of the underlying dispersion interactions were quantified. The second publication investigates the influence of solvents on weak noncovalent interactions between aromatic moieties. Using a cyclooctatetraene (COT)-based molecular balance, the simplest aromatic system, the benzene dimer, was first considered. In the third publication, it was subsequently observed how the solvent effect changes upon introduction of polar groups. Finally, the fourth publication shows how the obtained insights can be used to critically re-evaluate established reaction mechanisms. In the case of the Johnson–Corey–Chaykovsky epoxidation, it was demonstrated that the observed selectivity is not primarily governed by steric repulsion, as long assumed, but is instead significantly influenced by attractive London dispersion interactions between sterically demanding substituents.