Are the absolute configurations of 2-(1-hydroxyethyl)-chromen-4-one and its 6-bromo derivative determined by X-ray crystallography correct? A vibrational circular dichroism study of their acetate derivatives

Abstract The vibrational circular dichroism (VCD) spectra of the acetate derivative, 3 , of 2-(1-hydroxyethyl)-chromen-4-one, 1 , and the acetate derivative, 4 , of 6-bromo-2-(1-hydroxyethyl)-chromen-4-one, 2 , in the C O stretching region are reported. Density functional theory (DFT) predictions of the VCD spectra of the C O stretching modes of ( R )- 3 and ( R )- 4 are in excellent agreement with the experimental spectra for (+)- 3 and (+)- 4 , demonstrating that the absolute configurations of both molecules are ( R )-(+)/( S )-(−). Since acetylation of (+)- 1 and (+)- 2 yields (+)- 3 and (+)- 4 , this in turn leads to ( R )-(+)/( S )-(−) for both 1 and 2 . The absolute configurations of (−)- 1 and (−)- 2 were previously determined using X-ray crystallography to be R and S , respectively. Our results lead to the conclusion that the previously reported absolute configuration of 1 is incorrect. This work is the first to apply the ‘conformational rigidification via chemical derivatisation’ methodology to the determination of absolute configuration using VCD spectroscopy and illustrates its utility in determining the absolute configurations of chiral alcohols and, by extension, other classes of chiral molecules containing flexible functional groups.