Conformational characterization of a camphor-based chiral γ-amino alcohol

Experimental 1H chemical shift analysis for the camphor-based chiral γ-amino alcohol 2 shows a difference of 0.9 ppm for the two diastereotopic hydrogens H11a and H11b. In contrast, for the exo adduct (1) and its acetate (3) these hydrogens have very similar chemical shifts. DFT calculations followed by NBO analysis show that these differences in chemical shifts arise as a consequence of an intramolecular hydrogen bond OH⋯N in 2, which restricts its conformational mobility. In the most stable conformer of 2, the interaction of the nitrogen lone-pair with the vicinal σ*(CH11a) antibonding orbital shifts that hydrogen downfield by 0.9 ppm. This is confirmed by experimental NMR studies based on NULL.