2-Cyano-2-indolylpropanoic acid as a chiral derivatizing agent for the absolute configuration assignment of secondary alcohols and primary amines by 1H NMR and VCD

Abstract

A convenient approach for the absolute configuration assignment of secondary alcohols in the (8R,1′R,2′S,5′R)-15,25, (8S,1′R,2′S,5′R)-15,25, (8R,1′R)-21–24, and (8S,1′R)-21–24 ester series, and of primary amines in the (8R,1′R)-32–37 and (8S,1′R)-32–37 amide series, by means of 1H NMR and VCD spectroscopy, using 2-cyano-2-indolylpropanoic acid as a chiral derivatizing agent is presented. DFT calculations were carried out to demonstrate the anisotropic effect of the indole skeleton on the chiral alcohol or the amine fragment. Vibrational circular dichroism (VCD) measurements of the above series indicated a VCD bisignated couplet resulting from the interaction of the ester carbonyl group and the CN group. The absolute configuration assignments were further tested by X-ray diffraction analysis.