Conformational schemes: An available tool for the assignment of NMR-measured barriers, demonstrated with the example of crowded piperidines

MM3-derived full conformational schemes are proposed as a powerful and convenient tool for the currently problematic assignment of NMR-measured barriers for flexible systems that possess more than one type of independent intramolecular motion. Hindered piperidines were chosen as a molecular model with seven possible intramolecular dynamic processes. The free energies of activation for methyl group topomerization in 1,2,2,5,5-pentamethyl-, 1-ethyl-2,2,6,6-tetramethyl-, and 1-butyl-2,2,6,6-tetramethylpiperidines were determined at different temperatures by means of line-shape analysis of ¹³C NMR spectra. Schemes of conformational transformations for the N-Me and N-Et compounds were created with MM3-based methodology. These schemes permit the assignment of the measured barriers to ring inversion for the N-Me compound and to ring inversion - nitrogen inversion, ring inversion, and C - N rotation for the N-Alk^primary piperidines (for the N-Et and N-Pr derivatives the experimental barriers had previously been attributed to isolated C - N rotation only). A unique dynamic process for tertiary amines, isolated nitrogen inversion, is described for the N-alkylpiperidines with an N-substituent bulkier than Me.