Fig. 1. (A) Transition states obtained through metadynamics simulations for: (I) the non-activated CF₃SO₂F-triflylation of piperidine in acetonitrile, (II) the DMAP-activated CF₃SO₂F-triflylation of piperidine in acetonitrile, (III) the Et₃N-activated CF₃SO₂F-triflylation of piperidine in acetonitrile and (IV) the non-activated CF₃SO₂F-triflylation of piperidine in acetonitrile including two molecules of piperidine. In all cases, electron displacement is schematically illustrated using green arrows. During the simulations, Gaussian shaped potentials were placed along two coordination numbers, resulting in a free energy surface and Helmholtz free energy of activation (ΔF^‡). Simulations were performed in triplicate. (B) Triflylation of phenylpiperazine as model reaction varying the base, solvent and relative amounts of substrate and CF₃SO₂F. Isolated yields are provided unless stated otherwise. [a] ¹⁹F NMR yield relative to int. std. after 72 h reaction time. (C) NCI analyses were performed on the transition states of the DMAP-mediated CF₃SO₂F triflylation (II, green) and Et₃N-mediated CF₃SO₂F triflylation (III, red). Analyses were performed in absence of the solvent to focus on the noncovalent interactions present in and between the reactive species. Top; 3D NCI isosurfaces (s = 0.5) visualized for both reactive systems. An RGB-scale is used to differentiate between repulsive (red) and attractive (green) interactions, set from −0.005 a.u. to 0.005 a.u. For the DMAP-mediated triflylation, a non-classical CH⋯O hydrogen bond is observed as an attractive blue surface, which connects DMAP with CF₃SO₂F (purple arrow). Bottom; an overlay plot of s against ρ sign(λ₂) is presented for both NCI analyses.