Separation of Diastereomers by Distillation—A New Procedure for the Synthesis of Optically Active Heterocyclic Carboxylic Acids

Resolution by distillation, in contrast to classical resolution by recrystallization, may be easy to perform. In the case of heterocyclic carboxylic acids 1 (X = O, S. n = 1,2), the diastereomeric amino acid amides 2, which differ in boiling point by 7 K under reduced pressure, were separated by fractional distillation. Remarkably. both enantiomers of 2-tetrahydrofurancarboxylic acid 1a (X = 0, n = 1) were obtained by the distillation of the diastereomers of 2a (R = iPr. R′ = Me) with 99% optical purity.