Asymmetric Synthesis Using Chiral Lithium Alkoxytrialkylaluminates: Obtention of (2S)-2-Hydroxy-2-phenyl-4-methylpentanoic Acid with 85percent Optical Purity

Article abstract of DOI:10.1021/jo00221a016

The chiral reagent prepared by mixing equimolecular amounts of triisobutylaluminium and lithium alcoholate of (+)-Darvon alcohol reacts readily in hexane solvent with methyl phenylglyoxylate to give the expected α-isobutyl α-hydroxy ester in 95percent chemical yield with no significant reduction byproduct, and best optical yields are achieved at 0 deg C and high dilution (0.04 M) in hexane.Upon saponification of the ester, (2S)-2-hydroxy-2-phenyl-4-methylpropanoic acid is obtained in 85percent enantiomeric excess.Reacting the lithium alkoxytriethylaluminate and lithium alkoxytri-n-butylaluminate with the same α-keto ester provided confirmatory evidence for the influence of dilution on the extent of asymmetric induction.