Stereoselective synthesis of β,ε-dihydroxy-α-amino acids by ring opening of 4,5-dihydroisoxazolyl derivatives

Article abstract of DOI:10.1016/j.tetasy.2008.11.034

Enantiomerically pure β-(4,5-dihydroisoxazol-3-yl)-substituted β-hydroxy-α-amino acids were synthesised stereoselectively by means of an addition reaction between (5,5-disubstituted-4,5-dihydroisoxazol-3-yl)-carbaldehydes and (R)-(+)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (Schoellkopf's reagent) as a chiral auxiliary. The addition gave mixtures of only two adducts with high diastereoselectivity. The steric configuration of the major diastereoisomer was assigned on the basis of spectroscopic data and the accepted model for the aldol condensation of the Schoellkopf's reagent. The subsequent acid-catalysed hydrolysis of the pyrazine ring led to a mixture of β-(4,5-dihydroisoxazol-3-yl)-β-hydroxy-α-amino methyl esters together with a mixture of two partially hydrolysed dipeptides. The final reductive cleavage of the 4,5-dihydroisoxazole ring of these compounds made it possible to obtain the methyl esters of β,ε-dihydroxy-γ-oxo-ε,ε-disubstituted α-amino acid derivatives.