O-Acetylmandelic acid as a reliable chiral anisotropy reagent for the determination of absolute configuration of alcohols

Abstract

NMR analyses of O-acetylmandelate (OAM) esters of a variety of crowded and conformationally locked cyclitol derivatives and other alcohols were carried out to examine the reliability of the use of OAM as a chiral anisotropy reagent (CAR) for the determination of the absolute configuration of an alcohol. These experiments showed that OAM can be used as a reliable CAR even in the case of sterically crowded alcohols, but the use of this method in conformationally locked alcohols should be skeptical. Although OAM is a frequently used chiral auxiliary for the resolution of cyclitol derivatives, the absolute configuration of the resolved alcohol is usually determined by converting it to a derivative of already known absolute configuration. The present study suggests that just the NMR analysis of the resolved diastereomers is sufficient enough to deduce the absolute configuration of these resolved cyclitol derivatives to determine their absolute configurations. Many literature examples where OAM is used for the resolution of different alcohols are used to generalize the fact that OAM is more reliable than other frequently used CARs such as methoxy trifluoromethyl phenyl acetic acid (MTPA), methoxy phenyl acetic acid (MPA) and mandelate.