Convenient synthesis of propane aminophosphonic acids, aminodiphosphonic acids and their structural analogues, mediated by azetidinium salts

• Published in: Tetrahedron Vol. 55; no. 41; pp. 12211 - 12226
• Main Authors: Bakalarz, A, Heliński, J, Krawiecka, B, Michalski, J, Potrzebowski, M.J
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 08.10.1999; Elsevier
• Subjects: azetidines; Chemistry; Chemistry, Organic; molecular modeling; NMR; phosphine oxides; phosphonic acids and derivatives; Physical Sciences; Science & Technology; phosphine oxides; NMR; molecular modeling; phosphonic acids and derivatives; azetidines; SUBSTITUENT; TRANSITION-METAL COMPLEXES; LIGANDS; PHOSPHINES; COORDINATION; COUPLING-CONSTANTS
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/S0040-4020(99)00698-5

The reactions of azetidinium salts with phosphorus nucleophiles R 2P(O)H have been investigated. Treatment of O-benzyl-N,N-diethyl-3-hydroxyazetidinium salt 2 with R 2P(O)H in the presence of sodium hydride gave the corresponding γ-N,N-diethylamino-β-benzyloxypropylphosphonate 6a or phosphine oxide 6b. After debenzylation γ-N,N-diethylamino-β-hydroxypropylphosphonate 3a and phosphine oxide 3b were obtained. The compound 6a was converted into its sulfonate ester 8 which underwent elimination to yield 4. The structure 4 has been employed in Michael addition of R 2P(O)H to form compounds 5 containing two phosphorus centers. Further compounds of type 3 have been transformed into compounds 5 by reaction with R 2P(O)H in the presence of 1.1 equivalents of NaH in boiling toluene. Finally, azetidinium salts 1 have been converted into compounds 5a by reaction with two equivalents of R 2P(O)H in the presence of 2.1 equivalents of NaH. Molecular mechanics with implementation of the Allinger MM2 force field and semiempirical AM1 and PM3 methods were used to investigate structures 5d and 5f. Graphic