Determination of absolute configurations of β-or γ-methyl substituted secondary alcohols by NMR spectroscopy

Abstract

A new method has been developed for determining the absolute configurations of acyclic β- or γ-methyl substituted secondary alcohols using their 2NMA esters. The 1H-NMR spectra of (R)- and (S)-2NMA esters of model compounds were measured, and Δδ values (δ(R-ester) - δ(S-ester) for the corresponding protons were compared between syn and anti compounds. Threshold values important to judging the relative stereochemistry of the two chiral centers bearing methyl and hydroxy groups were obtained. The absolute configuration of the chiral bearing a secondary hydroxy group is easily determined based on the sign of Δδ values as in the MTPA method and thus in the present study it was also possible to clearly determine the absolute configuration of the chiral center bearing a methyl group.