Studies on organophosphorus compounds 101. A facile synthetic route to trifluoromethylated aminophosphonic acids and phosphonopeptides

A series of dialkyl 1-(N-substituted amino)-2,2,2-trifluoroethylphosphonates was synthesized by Arbuzov-type reactions involving an N-substituted trifluoromethylimidoyl chloride and the appropriate trialkyl phosphite. The resulting C=N bond was successfully hydrogenated by NaBH₄CN treatment. The subsequent deprotection of the amino group was conducted either by hydrogenolysis with Pd black or by use of cerium ammonium nitrate, depending on the structure of the substituent on the amino function. The free amino group thus obtained underwent a coupling reaction with an aminoacyl chloride in the usual manner. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:139–146, 1998