Enantiomeric impurities in chiral catalysts, auxiliaries and synthons used in enantioselective synthesis

Abstract

Eighty three popular chiral reagents that are used to synthesize a wide variety of compounds of high enantiomeric purity were analyzed in order to determine their enantiomeric composition. Included in the study are chiral catalysts for stereoselective reductions, epoxidations and hydrocarboxylations; chiral auxiliaries including a variety of oxazolidinones; a wide variety of chiral synthons and chiral resolving agents. Enantiomeric impurities were found in all reagents. The reagents were categorized by the level of their enantiomeric contaminants. The four level ranges were: 0.01% to 0.1%, 0.1% to 1%, 1% to 10% and >10%. Over half of the chiral reagents tested had enantiomeric impurities at levels >0.1%. The batch to batch enantiopurity of a reagent from a single source was examined as well as the variation in the enantiopurity of the same reagent from different sources. Possible adverse aspects of having unknown quantities of enantiomeric impurities in stereoselective syntheses are mentioned.