NH-Polyfluoroalkyl іminophosphonates in the synthesis of α-amino-α-polyfluoroalkyl-γ-oxobutylphosphonic acids

• Main Authors: O. V. Stanko, Y. P. Yelenich, P. P. Onys’ko, Yu. V. Rassukana
• Format: Article
• Language: English
• Published: National University of Pharmacy (Kharkiv, Ukraine) 2019-05-01
• Series: Журнал органічної та фармацевтичної хімії
• Subjects: оptically active aminophosphonates; рolyfluoroalkylated aminophosphonic acids; іminophosphonates; stereoselective synthesis
• Online Access: http://ophcj.nuph.edu.ua/article/view/ophcj.19.967/170513

Aim. To develop the preparative method for the synthesis of optically active α-amino-α-polyfluoroalkyl-γ-oxobutylphosphonic acids as new promising chiral building blocks. Results and discussion. It has been shown that the reaction of NH-polyfluoroalkyl aminophosphonates with acetone in the presence of a catalytic amount of L- or D-proline occurs stereoselectively to give enantiomerically enriched (R)- or (S)-α-amino-γ-oxophosphonates, respectively. The resulting optically active phosphonates were converted into water-soluble α-amino-γ-oxophosphonic acids isolated in the individual form as hydrochlorides. Experimental part. By the reaction of рolyfluoroacetonitriles with diethyl phosphite in the presence of triethylamine the series of NH-рolyfluoroalkyl іminophosphonates were synthesized. They undergo the prolinecatalysed reaction with acetone to form optically active α-amino-α-polyfluoroalkyl-γ-oxobutyl phosphonates. The latter were converted into the corresponding phosphonic acids by the reaction with hydrogen chloride. The structures of the compounds synthesized were confirmed by analytical and spectral NMR (1Н, 13С, 19F, 31Р) methods. Conclusions. Based on the proline-catalyzed reaction of NH-рolyfluoroalkyl іminophosphonates with acetone the preparative synthesis method for new chiral building blocks – α-amino-α-polyfluoroalkyl-γ-oxobuthylphosphonates and phosphonic acids has been developed.