Stereoelectronic interactions: A booster for ⁴ J_HF transmission

Long-range proton-fluorine coupling constants (ⁿ J_HF ) are helpful for the structure elucidation of fluorinated molecules. However, their magnitude and sign can change with the relative position of coupled nuclei and the presence of substituents. Here, trans-4-tert-butyl-2-fluorocyclohexanone was used as a model compound for the study of the transmission of ⁴ J_HF . In this compound, the ⁴ J_H6axF was measured to be +5.1 Hz, which is five times larger than the remaining ⁴ J_HF in the same molecule (⁴ J_H4F  = +1.0 Hz and ⁴ J_H6eqF  = +1.0 Hz). Through a combination of experimental data, natural bond orbital (NBO) and natural J-coupling (NJC) analyses, we observed that stereoelectronic interactions involving the π system of the carbonyl group are involved in the transmission pathway for the ⁴ J_H6axF . Interactions containing the π system as an electron acceptor (e.g., σ_C6H6ax  → π^*_C═O and σ_CF  → π^*_C═O ) increase the value of the ⁴ J_H6axF , while the interaction of the π system as an electron donor (e.g., π_C═O  → σ^*_CF ) decreases it. Additionally, the carbonyl group was shown not to be part of the transmission pathway of the diequatorial ⁴ J_H6eqF coupling in cis-4-tert-butyl-2-fluorocyclohexanone, revealing that there is a crucial symmetry requirement that must be fulfilled for the π system to influence the value of the ⁴ J_HF in these systems.