Nitrogen inversion barrier of 2-methyl-2-azabicyclo[2.2.1]heptane. The role of torsional strain in pyramidal inversion

Article abstract of DOI:10.1021/jo951940i

Low-temperature ¹³C NMR measurements indicate that the endo isomer of 2-methyl-2-azabicyclo-[2.2.1]heptane is about 0.3 kcal mol^-1 more stable than the exo isomer. Rate constants for inversion from the endo to exo isomer were determined by NMR line shape analysis. The inversion barrier, ΔG?, of 7.2 kcal mol^-1 is lower than that in model acyclic amines, despite an internal CNC bond angle that is less than the tetrahedral angle of 109.47°. Comparison with 7-methyl-7-azabicyclo-[2.2.1]heptane that has a small internal CNC angle and an unusually high barrier, as well as other cyclic and bicyclic amines, leads to the conclusion that torsional (eclipsing) strain plays a significant role along with angle strain in determining inversion barriers. Molecular mechanics calculations of the change in energy between pyramidal ground state and planar transition state account reasonably well for the observed barriers. New measurements of inversion barriers and their dependence on solvent are also reported for 2-methyl-2-azabicyclo[2.2.2]octane and l-methyl-4-piperidone.