Determining the absolute stereochemistry of secondary/secondary diols by 1H NMR:: Basis and applications

The absolute configuration of 1,2-, 1,3-, 1,4-, and 1,5-diols formed by two secondary (chiral) hydroxy groups can be deduced by comparison of the NMR spectra of the corresponding bis-(R)- and bis(S)-MPA esters. The correlation between the NMR spectra of the bis-ester derivatives and the absolute stereochemistry of the diol involves the comparison of the chemical shifts of the signals for substituents R-1/R-2 and for the hydrogens attached to the two chiral centers [H-alpha(R-1) and H-alpha(R-2)] in the bis-(R)- and the bis-(S)-ester and is expressed as Delta delta.(RS) Theoretical calculations [energy minimization by semiempirical (AM1), ab initio (HF), DFT (B3LYP), and Onsager methods, and aromatic shielding effect calculations] and experimental data (NMR and CD spectroscopy) indicate that in these bis-MPA esters, the experimental Delta delta(RS) values are the result of the contribution of the shielding/deshielding effects produced by the two MPA units that combine according to the actual stereochemistry of the diol. The reliability of these correlations is demonstrated with a wide range of diols of known absolute configuration derivatized with MPA and 9-AMA as auxiliary reagents. A simple graphical model that allows the simultaneous assignment of the two asymmetric carbons of a 1,n-diol by comparison of the NMR spectra (Delta delta(RS) signs) of its bis-(R)- and bis-(S)AMAA ester derivatives is presented.