London Dispersion Favors Sterically Hindered Diarylthiourea Conformers in Solution. (15th June 2022)

• Record Type: Journal Article
• Authors: Rummel, Lars; Domanski, Marvin H. J.; Hausmann, Heike; Becker, Jonathan; Schreiner, Peter R.
• Is Part Of: Angewandte Chemie. Volume 134:Number 29(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-15
• Subjects: Conformational Analysis -- Local Energy Decomposition -- Pauli Repulsion -- Symmetry-Adapted-Perturbation Theory -- σ–σ Interactions; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202204393
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : Steric crowding counterintuitively favors the folded and apparently more sterically hindered syn – syn conformer of N, N ′‐diphenylthiourea derivatives. Combined experimental and computational analyses identified London dispersion interactions to be the decisive factor favoring the conformer equipped with bulky dispersion energy donor groups.