Absolute Configuration Assignment from Optical Rotation Data by Means of Biphenyl Chiroptical Probes.

Abstract

A non-empirical approach for the assignment of the absolute configuration of chiral 2-alkyl-substituted carboxylic acids and primary amines by [α]D measurements has been developed. The method requires the conversion of the chiral acids or amines into the corresponding 4,4'-disubstituted biphenylamides or biphenylazepines, respectively. In these derivatives a central-to-axial chirality transfer induces a preferred torsion in the biphenyl moiety revealed by the sign of the biphenyl A band in the ECD spectrum. By 4,4'-substitution on the biphenyl moiety a redshift of the A band is obtained, leading to an increase of its relative contribution to optical rotation. This allows to reliably establish a direct correlation between the [α]D sign, the biphenyl twist and, then, the substrate absolute configuration. This approach thus constitutes a really practical and reliable method to assign the absolute configuration of chiral carboxylic acids and primary amines by simple and straightforward [α]D measurement, readily obtainable by a routine instrumentation like the polarimeter.