Synthesis and Separation of Diastereomeric Imino Alcohol Derivatives of Chiral Phthalides: A Method for Assignment of Phthalide Absolute Configurations

Article abstract of DOI:10.1021/jo00390a012

Representative members of a series of chiral type 1 phthalides were converted with Lawesson's reagent to the corresponding thionophthalides.On treatment with any of several configurationally known chiral amino alcohols in the presence of mercuric trifluoroacetate, diastereomeric imino alcohols are afforded.These prove to be readily separable by chromatography on either silica or chiral stationary phases derived from the N-3,5-dinitrobenzamides of (R)-phenylglycine or (S)-leucine.Both the elution order of these diastereomers from silica and their 1H NMR chemical shift differences may be related to relative/absolute configurations.Hydrolysis of the separated imino alcohol diastereomers affords configurationally established phthalide enantiomers.On the basis of their CD spectra, it is concluded that the enantiomers of the entire series of phthalides elute from the chiral stationary phases in a uniform order