Stereoelectronic interactions: A booster for ⁴ J_HF transmission

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Spectroscopy

Background:

• Long-range proton-fluorine coupling constants (nJHF) are valuable for determining the structure of fluorinated organic compounds.
• The magnitude and sign of nJHF can vary based on the spatial arrangement of coupled nuclei and the presence of substituents, complicating structural analysis.

Purpose of the Study:

• To investigate the transmission pathways of four-bond proton-fluorine coupling constants (4JHF) in fluorinated cyclohexanone derivatives.
• To elucidate the role of stereoelectronic interactions, particularly those involving the carbonyl group's π system, in modulating 4JHF values.

Main Methods:

• Experimental measurement of 4JHF in trans-4-tert-butyl-2-fluorocyclohexanone.
• Natural Bond Orbital (NBO) analysis to probe electronic structure and bonding interactions.
• Natural J-coupling (NJC) analysis to correlate electronic interactions with coupling constants.

Main Results:

• A significantly larger 4JHF (5.1 Hz) was observed for the axial proton at C6 (4J H6axF) compared to other 4JHF values in the same molecule (1.0 Hz).
• NBO/NJC analyses revealed that stereoelectronic interactions with the carbonyl π system, acting as an electron acceptor or donor, influence the magnitude of 4J H6axF.
• The carbonyl group was not involved in the transmission pathway for the diequatorial 4JHF in the cis isomer, highlighting a critical symmetry requirement.

Conclusions:

• The carbonyl group's π system plays a key role in transmitting 4JHF, but its influence is dependent on specific stereoelectronic interactions and molecular symmetry.
• Understanding these interactions is essential for accurately interpreting nJHF data in the structural elucidation of complex fluorinated molecules.