DETERMINATION OF THE ABSOLUTE-CONFIGURATION OF SECONDARY ALCOHOLS WITH HOREAUS METHOD INCLUDING ENANTIOSELECTIVE GAS-CHROMATOGRAPHY

The reaction of optically active secondary alcohols with excess of rac emic 2-phenylbutyric acid anhydride in pyridine proceeds at different rates to the diastereoisomeric esters (kinetic partial resolution). Ac cording to Horeau(1) the (unknown) absolute configuration of the alcoh ol can be derived from the optical rotation of the remaining excess of 2-phenylbutyric acid in the reaction mixture. Measuring the optical r otation may be very difficult in cases of small absolute rotation valu es and may be inaccurate due to the necessity to completely remove all chiral impurities. The application of Horeau's method is greatly faci litated by gas chromatographic determination of the enantiomeric ratio of the remaining 2-phenylbutyric acid after methylation using a short capillary column with akis(2,6-di-O-methyl-3-O-pentyl)-beta-cyclodext rin as a chiral stationary phase. Baseline resolution of the enantiome rs is achieved after approximately 10 min of retention time. Due to th e high selectivity of capillary gas chromatography the probability of impurities in the mixture to interfere with the measurement of the ena ntiomeric ratio is extremely low. (C) 1994 Wiley-Liss, Inc.