Crowded piperidines with intramolecularly hydrogen-bonded nitrogen: Synthesis and conformation study

2,2,6,6-Tetramethyl substituted piperidines with a β-branched N-alkyl substituent were synthesized by the photoreaction of N-Me precursors with ketones. The main conformation features of these sterically-hindered amines (established by NMR and IR spectroscopy) are a ring in the chair form, an eclipsed conformation for the N-substituent and an intramolecular OH···N bond. High barriers for the geminal substituent topomerization were measured for these piperidines at different temperatures by means of line-shape analysis of the temperature-dependent ¹³C and ¹H NMR spectra. An MM3-derived conformation scheme indicated that, for one of the studied analogues, the rotation of the N-substituent determines a slow topomerization rate. A new mechanism of nitrogen inversion - a concerted hydrogen-bond dissociation/nitrogen inversion process - is considered for hydrogen-bonded amines.