Stereoselective syntheses of protected β-hydroxy-α-amino acids using (arylthio)nitrooxiranes

Abstract

The scope and limitations of a method for the stereocontrolled synthesis of a range of protected β-hydroxy-α-amino acids have been established. The method comprises condensation of a chiral, enantiomerically pure aldehyde 6 with (4-methylphenylthio)nitromethane 7 to form a 1-arylthio-1-nitroalkene 8; stereoselective epoxidation of this alkene with a metal alkyl peroxide; and stereospecific reaction of the arylthionitrooxirane with a nitrogen nucleophile to give an α-amino thioester. This method has been employed in the synthesis of protected derivatives of both diastereoisomers of threonine 1 and 2, and of β-hydroxyleucine 3 and 4 and a synthesis of the anti-diastereoisomer of β-phenylserine 5.