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 pi system of the carbonyl group are involved in the transmission pathway for the (4)J(H6axF). Interactions containing the pi system as an electron acceptor (e.g., sigma(C6-H6ax) -> pi*(CO) and sigma(C-F) -> pi*(CO)) increase the value of the (4)J(H6axF), while the interaction of the pi system as an electron donor (e.g., pi(CO) -> sigma*(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 pi system to influence the value of the (4)J(HF) in these systems.