ENANTIOSELECTIVE SYNTHESIS OF 2-ALKYL SUBSTITUTED CYSTEINES

Treatment of the N-formyl derivative of the thiazolidine adduct derived from (R)-cysteine methyl ester hydrochloride and pivalaldehyde, with LDA-DMPU at -90-degrees-C, followed by reaction with iodomethane produces the corresponding methylated thiazolidine containing the methyl and t-butyl groups virtually exclusively anti- to one another. Hydrolysis in the presence of 5M HCl then affords (R)-2-methylcysteine hydrochloride in excellent yield and enantiometic purity. A range of other 2-alkyl substituted cysteines of excellent optical purity are prepared by this modification of Seebach's ''self-reproduction of chirality'' protocol.