COMMENTS ON THE PUTATIVE STEREOSELECTIVITY IN CYSTEINE-ALDEHYDE REACTIONS - SELECTIVE C(2) INVERSION AND C(4) EPIMERIZATION IN THIAZOLIDINE-4-CARBOXYLIC ACIDS

(R)-and (S)-cysteine react with benzaldehyde and p-tolualdehyde nonstereospecificaliy to produce 1:1 mixtures of C(2) epimeric 2-aryl-1,3-thiazolidine-4-carboxyUc acids, 1-3. N-Acetylation, using acetic anhydride/pyridine at 25 °C or acetic anhydride/water at 100 °C, is accompanied by selective inversion at C(2) of the 2,4-cis and 2,4-trans epimers, respectively. No epimerization occurs at C(4) as evidenced by Raney-Ni desulfurization of both the 2(R)-and 2(S)-phenyl-3-acetyl-1,3-thiazolidine-4(R)-carboxylic acid methyl esters, 12 and 14. On the other hand, selective epimerization at C(4) takes place when 1,5, or 8 are treated with acetic anhydride at 100 °C. Mechanistic proposals, supported by deuterium incorporation measurements and product analyses, are advanced for these epimerization reactions. It is demonstrated that complete stereospecificity in the reaction between (R)-cysteine and p-tolualdehyde was erroneously implied on the basis of misinterpreted 1H NMR spectra. © 1979, American Chemical Society. All rights reserved.