Conversion of nitriles to 1-aminophosphonic acids and preparation of phosphahomocysteines of high enantiomeric excess

Abstract

<p></p> <p>A variety of nitriles was reduced to diisobutylaluminum salts of aldimines, to which diisopropyl phosphite was added. The corresponding 1-aminophosphonates were either deprotected to give racemic 1-aminophosphonic acids or reacted with Boc₂O to yield <i>N</i>-Boc-protected 1-aminophosphonates. The enantiomers of 2-benzylthio-1-(<i>t</i>-butoxycarbonylamino)propylphosphonate were obtained from the racemate by chiral HPLC and converted to phosphonic acid analogs of (<i>R</i>)- and (<i>S</i>)-homocysteine, (<i>R</i>)- and (<i>S</i>)-2-aminobutyric acid and (<i>S</i>)-methionine, all of ee >97% as determined by chiral HPLC.</p