Electrostatic CH−π Interactions Can Override Fluorine Gauche Effects To Exert Conformational Control

• Published in: Chemistry : a European journal 2023-01, Vol.29 (6), p.e202203139-n/a
• Main Authors: Emenike, Bright U., Farshadmand, Amiel, Zeller, Matthias, Roman, Armando J., Sevimler, Arzu, Shinn, David W.
• Format: Article
• Language: English
• Subjects: aromatic interactions; Chemistry; coupling constants; Crystallography; Electrostatic properties; Fluorine; gauche effects; Hammett constants; Magnetic resonance spectroscopy; NMR; NMR spectroscopy; Nuclear magnetic resonance
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202203139

Fluorine gauche effects are conformational properties of 2‐fluoroethanes often applied in modern molecular designs. However, the physical origins of fluorine gauche effects are not well understood, with the consensus favoring the established hyperconjugation theory over an emerging electrostatic model. Using a series of model systems, we show that a shift to fluorine gauche effects can be influenced by intramolecular CH⋅⋅⋅π aromatic interactions, a through‐space event. Modulating the π‐ring (forming the aromatic interaction) with substituent groups resulted in a linear Hammett relationship, thus indicating that the CH⋅⋅⋅π interaction has electrostatic features. For instance, attaching a nitro group (an electron‐withdrawing substituent) to the π‐ring weakened the CH⋅⋅⋅π interaction and led to a gauche preference, whereas an anti conformer is preferred with amine as substituent. The experimental results performed by using proton NMR spectroscopy are corroborated by gas‐phase DFT calculations and solid‐state X‐ray crystallography. Are the fluorine gauche effects in fluoroethyl systems controlled electrostatically or by hyperconjugation? This experimental study shows that electrostatic forces from CH⋅⋅⋅π interactions (between polar CH2F protons and an adjacent aromatic ring) can override an inherent fluorine gauche effect to exert conformational control over fluoroethyl systems.