Synthesis of new α or γ-functionalized hydroxymethylphosphinic acid derivatives

The syntheses of new gamma-ethoxycarbonyl- and alpha-amino-alkyl hydroxymethylphosphinic acid derivatives are described. These compounds were conveniently prepared by Michael addition or Kabachnik-Fields reaction of an original precursor, ethyl benzyloxymethyl hydrogenophosphinate, respectively to alpha,beta-unsaturated esters using a basic activation or to imines. Selective deprotection of the alcohol function was achieved by hydrogenolysis on Pd/C, whereas lithium bromide was used to selectively cleave the phosphinate ester group. Acidic hydrolysis readily gave the free hydroxymethylphosphinic acids. (C) 2003 Elsevier Ltd. All rights reserved.