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

Experimental H-1 chemical shift analysis for the camphor-based chiral gamma-amino alcohol 2 shows a difference of 0.9 ppm for the two diastereotopic hydrogen s H-11a and H-11b. 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 O-(HN)-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 sigma*(C-H-11a) antibonding orbital shifts that hydrogen downfield by 0.9 ppm. This is confirmed by experimental NMR studies based on NULL. (c) 2006 Elsevier B.V. All rights reserved.