A method for the synthesis of unsymmetric bisphosphoric analogs of α-amino acids.

Herein, we describe the first universal strategy for the synthesis of unsymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogs of -protected 1-aminobisphosphonates. The proposed user-friendly procedure, based on a one-pot reaction of the α-ethoxy derivatives of phosphorus analogs of protein and non-protein α-amino acids with triphenylphosphonium tetrafluoroborate and an appropriate phosphorus nucleophile (diethyl phenylphosphonite or methyl diphenylphosphinite), provides good to very good yields of 53-91% under mild catalyst-free conditions (temperature: rt to 40 °C, time: 1 to 6 hours). The progress of the transformation, running through the corresponding phosphonium salt as a reactive intermediate, was monitored by P NMR spectroscopy, which is a convenient tool for the identification of the transient species formed here.