Investigation of Readily Available Chiral Compounds for Preparative Scale Resolutions

Abstract

Diastereoisomeric esters were formed by reaction of racemic carboxylic acids with the readily available hydroxy lactone derivatives, 2,3-O-isopropylidene-D(+)-ribono-l,4-lactone, D(-)-2- hydroxy-3,3-dimethylbutyro-1,4-lactone (D(-)-pantolactone) and 1,2-O-isopropylidene-(+)-α-D-glucofuranurono-6,3-lactone. In all cases separation of the diastereoisomeric esters was achieved by crystallization and/or chromatography. Purity of the diastereoisomers could be determined by h.p.l.c. or by 1H n.m.r. Hydrolysis under mild basic conditions followed by treatment with acid gave optically pure carboxylic acids. The facile separation by crystallization and/or chromatography of diastereoisomers prepared from racemic endo-1,4,5,6,7,7-hexachlorobicyclo[2.2.l]hept-5-ene-2-carboxylic acid suggested that the resolved acid may be useful as a resolving agent. This was shown by separation of diastereoisomers formed from the resolved acid and racemic 1-(3′-phenoxyphenyl)prop-2- yn-1-ol and racemic 1-cyano-1-(3'-phenoxypheny1)methanol respectively. Optically pure 1-(3'-phenoxypheny1)prop-2-yn-1-ol was obtained by hydrolysis of the separated diastereoisomers.