DOI: https://doi.org/10.24959/ophcj.19.967

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

O. V. Stanko, Y. P. Yelenich, P. P. Onys’ko, Yu. V. Rassukana

Abstract


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.


Keywords


оptically active a-aminophosphonates; рolyfluoroalkylated aminophosphonic acids; іminophosphonates; stereoselective synthesis

References


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Kafarski, P., Lejczak, B. (1991). Biological activity of aminophosphonic acids. Phosphorus, Sulfur, Silicon and related elements, 63 (1–2), 193–215. https://doi.org/10.1080/10426509108029443

Mucha, A., Kafarski, P., Berlicki, L. (2011). Remarkable potential of the β–aminophosphonate/phosphinate structural motif in medicinal chemistry. Journal of Medicinal Chemistry, 54 (17), 5955–5980. https://doi.org/10.1021/jm200587f

Romanenko, V. D., Kukhar, V. P. (2012). 1–Amino–1,1–bisphosphonates. Fundamental syntheses and new developments. Arkivoc, 2012 (4), 127–166. https://doi.org/10.3998/ark.5550190.0013.411

Rassukana, Yu. V., Yelenich, I. P., Synytsya, A. D., Onys`ko, P. P. (2014). Fluorinated NH–iminophosphonates and iminocarboxylates : novel synthons for the preparation of biorelevant a-aminophosphonates and carboxylates. Tetrahedron, 70 (18), 2928–2937. https://doi.org/10.1016/j.tet.2014.03.030

Onys’ko, P., Rassukana, Y., Kolotylo, M., Sinitsa, O., & Pirozhenko, V. (2007). α–Iminotrifluoroethylphosphonates: The First Representatives of N–H Imidoyl Phosphonates. Synthesis, 2007 (17), 2627–2630. https://doi.org/10.1055/s-2007-983838

Rassukana, Y. V., Yelenich, I. P., Vlasenko, Y. G., & Onys’ko, P. P. (2014). Asymmetric synthesis of phosphonotrifluoroalanine derivatives via proline–catalyzed direct enantioselective CC bond formation reactions of NH trifluoroacetimidoyl phosphonate. Tetrahedron: Asymmetry, 25 (16-17), 1234–1238. https://doi.org/10.1016/j.tetasy.2014.07.007


GOST Style Citations


1. Kukhar, V. P. Aminophosphonic and Aminophosphinic Acids : Chemistry and Biological Activity / V. P. Kukhar, H. R. Hudson // John Wiley & Sons : Chichester, 2000.

2. Kafarski, P. Biological activity of aminophosphonic acids / P. Kafarski, B. Lejczak // Phosphorus, Sulfur, and Silicon. – 1991. – Vol. 63, Issue 1–2. – P. 193–215. https://doi.org/10.1080/10426509108029443

3. Mucha, A. Remarkable potential of the β–aminophosphonate/phosphinate structural motif in medicinal chemistry / A. Mucha, P. Kafarski, L. Berlicki // J. Med. Chem. – 2011. – Vol. 54, Issue 17. – P. 5955–5980. https://doi.org/10.1021/jm200587f

4. Romanenko, V. D. 1–Amino–1,1–bisphosphonates. Fundamental syntheses and new developments / V. D. Romanenko, V. P. Kukhar // Arkivoc. – 2012. – Vol. 2012, Issue 4. – P. 127–166. https://doi.org/10.3998/ark.5550190.0013.411

5. Fluorinated NH–iminophosphonates and iminocarboxylates : novel synthons for the preparation of biorelevant α–aminophosphonates and carboxylates / Yu. V. Rassukana, I. P. Yelenich, A. D. Synytsya, P. P. Onys`ko // Tet. – 2014. – Vol. 70, Issue 18. – P. 2928–2937. https://doi.org/10.1016/j.tet.2014.03.030

6. α–Iminotrifluoroethylphosphonates : The first representatives of N–H imidoyl phosphonates / Yu. V. Rassukana, M. V. Kolotylo, O. A. Sinitsa et al. // Synth. – 2007. – Issue 17. – P. 2627–2630. https://doi.org/10.1055/s-2007-983838

7. Asymmetric synthesis of phosphonotrifluoroalanine derivatives via proline–catalyzed direct enantioselective CAC bond formation reactions of NAH trifluoroacetimidoyl phosphonate / Yu. V. Rassukana, I. P. Yelenich, Yu. G. Vlasenko, P. P. Onys`ko // Tet. Asym. – 2014. – Vol. 25, Issue 16–17. – P. 1234–1238. https://doi.org/10.1016/j.tetasy.2014.07.007





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