New N-acyl- as well as N-phosphonoylmethyl- and N-phosphinoylmethyl-a-amino- benzylphosphonates by acylation and a tandem Kabachnik-Fields protocol

Diethyl alpha-benzylamino-and alpha-amino-benzylphosphonates obtained by the Kabachnik-Fields reaction were useful intermediates in the synthesis of other derivatives. Acylation of alpha-aminophosphonates with acyl chlorides led to the corresponding N-acyl species existing under a dynamic equilibrium of two conformers. Judging from the broad NMR signals, the sterically most crowded N-benzoyl-N-benzyl derivative suffered a hindered rotation around the N-C axis to the acyl carbon atom at 26 degrees C. Low temperature NMR measurements at -10 degrees C showed the presence of two distinct rotamers that were characterized. The other acylated alpha-amino-benzylphosphonates prepared revealed a less hindered rotation. Single crystal X-ray diffraction of the NH-propionyl species showed a dimer, in which the two molecules were held together by rare intermolecular PvO?HN bonds. On the other hand, substituted alpha-benzylamino-benzylphosphonates prepared by phospha-Mannich reactions were employed, as a new approach, in a second Kabachnik-Fields condensation by reaction with formaldehyde and dialkyl phosphites or secondary phosphine oxides to afford novel N-phosphonoylmethyl-and N-phosphinoylmethyl-alpha-amino-ben-zylphosphonates. The structure of the new products was confirmed by two-dimensional NMR spectroscopy. A symmetrical bis derivative was prepared in a diastereoselective manner. A related tris(phosphonoylmethyl )amine species was also synthesized.

Automated summary

Diethyl alpha-benzylamino- and alpha-amino-benzylphosphonates obtained by the Kabachnik-Fields reaction were useful intermediates in the synthesis of other derivatives. Acylation of alpha-aminophosphonates with acyl chlorides led to the corresponding N-acyl species existing under a dynamic equilibrium of two conformers. NMR measurements at different temperatures revealed hindered rotation in some derivatives.