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

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Physical Chemistry

Background:

• Fluorine gauche effects in 2-fluoroethanes are crucial in molecular design but their physical origins remain debated.
• Current consensus favors hyperconjugation theory, overlooking potential electrostatic contributions.

Purpose of the Study:

• To investigate the role of intramolecular CH⋅⋅⋅π aromatic interactions in fluorine gauche effects.
• To explore the electrostatic nature of these through-space interactions and their influence on molecular conformation.

Main Methods:

• Utilized a series of model systems to study fluorine gauche effects.
• Employed proton NMR spectroscopy for experimental analysis.
• Performed gas-phase Density Functional Theory (DFT) calculations and solid-state X-ray crystallography for corroboration.

Main Results:

• Demonstrated that intramolecular CH⋅⋅⋅π aromatic interactions can influence the preference for fluorine gauche effects.
• Showcased that modulating the aromatic ring with substituents (e.g., nitro, amine) alters the CH⋅⋅⋅π interaction strength.
• Observed a linear Hammett relationship, indicating electrostatic characteristics of the CH⋅⋅⋅π interaction.

Conclusions:

• Intramolecular CH⋅⋅⋅π aromatic interactions play a significant role in governing fluorine gauche effects.
• The electrostatic nature of CH⋅⋅⋅π interactions provides a new perspective on conformational preferences in fluorinated compounds.
• Findings challenge the sole reliance on hyperconjugation theory and highlight the importance of through-space interactions.