The prediction of the absolute stereochemistry of primary and secondary 1,2-diols by H-1 NMR spectroscopy: Principles and applications

摘要

The absolute configuration of 1,2-diols formed by a primary and a secondary (chiral) hydroxyl group can be deduced by comparison of the H-1 NMR spectra of the corresponding (R)- and bis-(S)-MPA esters (MPA = methoxyphenylacetic acid). This method involves the use of the chemical shifts of substituents L-1/L-2 attached to the secondary (chiral) carbon, and of the hydrogen atom linked to the chiral center (C alpha-H) as diagnostic signals. Theoretical (AM1, HF, and B3LYP calculations) and experimental data (dynamic and low-temperature NMR spectroscopy, studies on deuterated derivatives, constant coupling analysis, circular dichroism (CD) spectra, and NMR studies with a number of diols of known absolute configuration) prove that the signs of the MRS obtained for those signals correlate with the absolute configuration of the Delta delta(RS). A graphical model for the reliable assignment of the absolute configuration of a 1,2-diol by comparison of the NMR spectra of its bis-(R)- and bis-(S)-MPA esters is presented.