A NEW APPROACH TO THE SYNTHESIS OF BETA-HYDROXY-ALPHA-AMINO ACIDS USING (ARYLTHIO)NITROOXIRANES

2-(Arylthio)-2-nitrooxiranes, prepared by the nucleophilic epoxidation of 1-(arylthio)-1-nitroalkenes using anhydrous metal alkyl peroxides in tetrahydrofuran, react with aqueous ammonia to give alpha-amino thioesters in good yield, without significant formation of the primary amide by subsequent reaction of the thioester with ammonia. lit situ protection of the amino group is possible, leading to a range of protected derivatives. Diastereoselective epoxidation of 1-(arylthio)-1-nitroalkenes with an allylic, oxygen-substituted stereogenic center using metal alkyl peroxides is possible, and the sense of diastereoselectivity can be controlled simply by use of lithium or potassium as the counterion. Enhanced syn selectivity (15:1) in lithium tert-butyl peroxide mediated epoxidations can be achieved by using toluene as solvent. Use of potassium triphenylmethyl peroxide, rather than potassium tert-butyl peroxide, generally gives higher anti selectivity (12:1). Reactions of enantiomerically and diastereoisomerically pure 2-(arylthio)-2-nitrooxiranes with ammonia proceed stereospecifically with inversion of configuration, establishing a stereocontrolled route to beta-hydroxy-alpha-amino acids. Use of other nitrogen nucleophiles, for example amino acid esters, is also possible, leading to a stereospecific approach to a-amino dicarboxylic acids. Applications of this methodology, which constitutes a stereocontrolled Strecker reaction, to the synthesis of gamma-hydroxy threonine derivatives 19-22, polyoxamic acid (26), and the C-5 epimer of the sugar fragment of polyoxin C (27) are described.