The conformational analysis of saturated heterocycles. N-inversion in hindered piperidines

Results from a new dynamic n.m.r. method, applicable to heavily biased equilibria, and kinetically controlled protonation studies agree when applied to 1,2,2,6-tetramethylpiperidine, giving the free energy difference for N-inversion [ΔG°(1E→1A)] as 1–9± 0·2 at 213 K (d.n.m.r.) and 1·95 ± 0·1 kcal mol–1 at 293 and 373 K (kinetic protonation); the free energy of activation [ΔG‡(1E→1A)] is 11·0 ± 0·3 kcal mol–1 at 213 K.