The potentialities of condensation of α-ketophosphonates with primary amines for direct
synthesis of α-iminophosphonates have been revealed. Diesters of α-ketophosphonic acids react with
the primary amines by two competitive pathways: with a formation of α-iminophosphonates or a C-P
bond cleavage resulting in a hydrogen phosphonate and an acylated amine. In many cases, the latter
undesirable pathway is dominant, especially for more nucleophilic alkyl amines. Using metallic salts
of α-ketophosphonates avoids the C-P bond cleavage, allowing direct preparation of α-phosphorylated
imines by the reaction with primary amines. This strategy provides an atom economy single-stage synthesis
of iminophosphonates – precursors of bio relevant phosphorus analogs of α-amino acids. Methyl
sodium iminophosphonates, bearing aryl or heteryl substituents at the imino carbon atom exist in
solutions at room temperature as an equilibrium mixture of Z- and E-isomers. A configuration of the
C=N bond can be controlled by the solvent: changing the aprotic dipolar solvent DMSO-d6 by water
or alcohols leads to the change from a predominant Z-isomer to almost an exclusive E-form. In contrast,
diesters of the respective iminophosphonates exist in non-protic solvents predominantly in Econfiguration.
The solvent effect on E-Z stereochemistry is demonstrated by DFT calculations.
THE DIRECT PREPARATION OF CRYSTALLINE UROBILIN FROM BILIRUBIN