First resolution of (R,R)- and (S,S)-bis(1-hydroxyphenylmethyl)phosphinic acids via diastereomeric salt formation with enantiopure 1-phenylethylamines

The resolution of racemic bis(1-hydroxyphenylmethyl)phosphinic acid with enantiopure 1-phenylethylamines via diastereomeric salt formation was investigated. X-ray crystallographic analysis of the salt clearly revealed that (S)-1-phenylethylamine was an efficient resolving agent for obtaining the single enantiomer (R,R)-bis(1-hydroxyphenylmethyl)phosphinic acid. Resolving racemic bis(1-hydroxyphenylmethyl)phosphinic acid with (R)-2-phenylethylamine gave access to (S,S)-bis(1-hydroxyphenylmethyl)phosphinic acid in good yield.

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(S)-Hydroxy(phenyl)methyl[(S)-hydroxy(phenyl)methyl]phosphinic acidC14H15O4P[α]D20=-62.5 (c 1.80, CH3OH)Source of chirality: (R)-1-phenylethylamineAbsolute configuration: (S,S)

(R)-Hydroxy(phenyl)methyl[(R)-hydroxy(phenyl)methyl]phosphinic acidC14H15O4P[α]D20=+62.5 (c 1.80, CH3OH)Source of chirality: (S)-1-phenylethylamineAbsolute configuration: (R,R)