Molecular dynamics and NMR reveal the coexistence of H-bond-assisted and through-space J FH coupling in fluorinated amino alcohols.

The J FH coupling constants in fluorinated amino alcohols were investigated through experimental and theoretical approaches. The experimental J FH couplings were only reproduced theoretically when explicit solvation through molecular dynamics (MD) simulations was conducted in DMSO as the solvent. The combination of MD conformation sampling and DFT NMR spin-spin coupling calculations for these compounds reveals the simultaneous presence of through-space (TS) and hydrogen bond (H-bond) assisted J FH coupling between fluorine and hydrogen of the NH group. Furthermore, MD simulations indicate that the hydrogen in the amino group participates in both an intermolecular bifurcated H-bond with DMSO and in transmitting the observed J FH coupling. The contribution of TS to the J FH coupling is due to the spatial proximity of the fluorine and the NH group, aided by a combination of the non-bonding transmission pathway and the hydrogen bonding pathway. The experimental J FH coupling observed for the molecules studied should be represented as 4TS/1h J FH coupling.