Diazotization of S-Sulfonyl-cysteines

The Journal of Organic Chemistry 84(22), 15001-15007, DOI: 10.1021/acs.joc.9b02630

We report the preparation of enantiomerically enriched β-thio-α-hydroxy and α-chloro carboxylic acid and ester building blocks by diazotization of S-sulfonyl-cysteines. The thiosulfonate protecting group demonstrated resistance to oxidation and attenuation of sulfur’s nucleophilicity by the anomeric effect. The key transformation was optimized by a 22 factorial design of experiment, highlighting the unique reactivity of cysteine derivatives in comparison with aliphatic amino acids."