Determining the absolute stereochemistry of secondary/secondary diols by 1H NMR: basis and applications.
[structures: see text] 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 R1/R2 and for the hydrogens attached to the two chiral centers [H(alpha)(R1) and H(alpha)(R2)] in the bis-(R)- and the bis-(S)-ester and is expressed as delta deltaRS. 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 deltaRS 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 deltaRS signs) of its bis-(R)- and bis-(S)-AMAA ester derivatives is presented.
Freire
Félix
F
Departamento de Química Orgánica, Facultad de Química, and Unidad de RMN de Biomoléculas Asociada al CSIC, Universidad de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
Seco
José Manuel
JM
Quiñoá
Emilio
E
Riguera
Ricardo
R