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

GRAPHICAL ABSTRACT

ABSTRACT

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 N-Boc-protected 1-aminophosphonates. The enantiomers of 2-benzylthio-1-(t-butoxycarbonylamino)propylphosphonate were obtained from the racemate by chiral HPLC and converted to phosphonic acid analogs of (R)- and (S)-homocysteine, (R)- and (S)-2-aminobutyric acid and (S)-methionine, all of ee >97% as determined by chiral HPLC.

KEYWORDS:

• Nitriles
• 1-aminophosphonic acids
• phosphahomocysteine
• desulfurization
• enantiomeric excess
• chiral HPLC
• 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate

Acknowledgments

The authors thank S. Felsinger for recording NMR spectra, E. Macoratti for performing the chiral HPLC separation of (±)-6d, M. Abraham for the determination of the configuration of (+)-6d, and J. Theiner for combustion analyses.