Determination of the absolute configuration of secondary alcohols with Horeau's method including enantioselective gas chromatography

Abstract

The reaction of optically active secondary alcohols with excess of racemic 2-phenylbutyric acid anhydride in pyridine proceeds at different rates to the diastereoisomeric esters (kinetic partial resolution). According to Horeau the (unknown) absolute configuration of the alcohol can be derived from the optical rotation of the remaining excess of 2-phenylbutyric acid in the reaction mixture. Measuring the optical rotation may be very difficult in cases of small absolute rotation values and may be inaccurate due to the necessity to completely remove all chiral impurities. The application of Horeau's method is greatly facilitated by gas chromatographic determination of the enantiomeric ratio of the remaining 2-phenylbutyric acid after methylation using a short capillary column with heptakis(2,6-di-O-methyl-3-O-pentyl)-β-cyclodextrin as a chiral stationary phase. Baseline resolution of the enantiomers is achieved after approximately 10 min of retention time. Due to the high selectivity of capillary gas chromatography the probability of impurities in the mixture to interfere with the measurement of the enantiomeric ratio is extremely low. © 1994 Wiley-Liss, Inc.