Synthesis of (2R, 3S)- or (2S, 3AR)-2-amino-3-trifluoromethyl-3-hydroxy-alkanoic acid derivatives (threonine and allo-threonine analogs) from enantiopure 4,4,4-trifluoro-3-hydroxybutanoic acid

Article abstract of DOI:10.1016/0040-4020(95)00895-F

The title compounds are prepared from the readily available enantiopure 6-alkyl- or 6-aryl-2-tert-butyl-6-trifluoromethyl-1,3-dioxan-4-ones with cis disposition of the tert-butyl and trifluoromethyl groups. Lithium enolates of these dioxanones are added to di-tert-butyl-azo-dicarboxylate to give exclusively the hydrazino derivatives formed by electrophilic attack from the face opposite to the tert-butyl and trifluoromethyl groups. Methanolysis of the dioxanone ring, removal of the N-Boc groups, and hydrogenolysis of the hydrazine N, N bond give methyl esters of (2R, 3S)-2-amino-4,4,4-trifluoro-3-hydroxybutanoic, (2R, 3S)-2-amino-4,4,4-trifluoro-3-hydroxy-3-methyl-butanoic, (2R, 3S)-2-amino-3-trifluoromethyl-3-hydroxyheptanoic, and (2R, 3S)-2-amino-4,4,4-trifluoro-3-hydroxy-3-phenyl-butanoic acids in overall yields ranging from 10 to 50%. Copyright