London Dispersion Favors Sterically Hindered Diarylthiourea Conformers in Solution

Abstract

We present an experimental and computational study on the conformers of N,N′‐diphenylthiourea substituted with different dispersion energy donor (DED) groups. While the unfolded anti–anti conformer is the most relevant for thiourea catalysis, intramolecular noncovalent interactions counterintuitively favor the folded syn–syn conformer, as evident from a combination of low‐temperature nuclear magnetic resonance measurements and computations. In order to quantify the noncovalent interactions, we utilized local energy decomposition analysis and symmetry‐adapted perturbation theory at the DLPNO‐CCSD(T)/def2‐TZVPP and sSAPT0/6‐311G(d,p) levels of theory. Additionally, we applied a double‐mutant cycle to experimentally study the effects of bulky substituents on the equilibria. We determined London dispersion as the key interaction that shifts the equilibria towards the syn–syn conformers. This preference is likely a factor why such thiourea derivatives can be poor catalysts.

London Dispersion Stabilizes Chloro-Substituted cis-Double Bonds

“…A similar effect was observed in the conformational analysis of all-meta-substituted diphenylthiourea. 34 Azobenzene derivatives 35 as well as hierarchically assembled dinuclear titanium(IV) helicates 36 confirm the effect for longer alkyl chains. The highest stabilizing interaction in favor of the cis-alkene again is observed for the…”