HAT energy (kcal/mol) Rebound energy (kcal/mol) Release energy (kcal/mol) In our search for reasons explaining the difference between fluorination of hydrocarbons and drug-like molecules, we hypothesized that they may stem from the kinetic control of this reactions. Based on this hypothesis, we obtain 1D potential energy scans across the fluorination reaction coordinate (Figure ). We observe that for cyclohexane, the fluorination reaction barrier is ca. 7 kcal/mol and the C-F distance in the putative transition state structure is 2.50 Å (Figure ). However, for piperidine, we observe that the putative transition state occurs at a shorter C-F distance of 2.35 Å and with almost six times higher energy barrier than that of cyclohexane, ca. 40 kcal/mol (Figure ), which greatly exceeds the range of thermal fluctuations (~kT). We see that while the rebound and release reaction energies are comparable and slightly more favorable for cyclohexane, the reaction barrier for fluorination clearly suggests that fluorination of cyclohexane is strongly preferred whereas the fluorination of piperidine is prohibited (Figure ). The higher energy barrier could be a result of stabilization of the radical through the lone pair of nitrogen heteroatom. It could also be possible that fluorine forms a more stable complex with this substrate. Further computational studies are necessary to understand why the energy barrier for fluorination of piperidine -and, presumably, drug-like molecules -is so high.