A New Approach to the Synthesis of β-Hydroxy-α-amino Acids Using (Arylthio)nitrooxiranes

Article abstract of DOI:10.1021/jo00125a032

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 α-amino thioesters in good yield, without significant formation of the primary amide by subsequent reaction of the thioester with ammonia.In 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 diastereomerically pure 2-(arylthio)-2-nitrooxiranes with ammonia proceed stereospecifically with inversion of configuration, establishing a stereocontrolled route to β-hydroxy-α-amino acids.Use of other nitrogen nucleophiles, for example amino acid esters, is also possible, leading to a stereospecific approach to α-amino dicarboxylic acids.Applications of this methodology, which constitutes a stereocontrolled Strecker reaction, to the synthesis of γ-hydroxy threonine derivatives 19-22, polyoxamic acid (26), and the C-5 epimer of the sugar fragment of polyoxin C (27) are described.