Stereodynamics of ring and nitrogen inversion in spiroheterocycles. Conformational analysis of N-methylspiro[morpholine-3,2′-adamantane] and N-methylspiro[piperidine-2,2′-adamantane] using NMR spectroscopy and theoretical calculations

Abstract

Adamantane forces the N-methyl group of N-methylspiro[morpholine-3,2′-adamantane] 1 and N-methylspiro[piperidine-2,2′-adamantane] 2 to adopt an axial orientation and to undergo a slow enantiomerization as depicted by dynamic ¹H and ¹³C NMR spectroscopy. The observed enantiomerization freezes below 0 °C as evidenced by the fully resolved protons and carbons of adamantane in NMR spectra. The observed resonances are interpreted using 2D NMR spectroscopy. Interconversion between the two enantiomeric forms is demonstrated by exchange spectroscopy (EXSY). The activation energy at the coalescence point is calculated from the ¹³C NMR spectra and found to be 14.3 and 15.2 kcal mol^–1 for molecules 1 and 2, respectively. Theoretical calculations suggest a mechanism of interconversion where the significant transition state is the one separating two twist-boat forms.