Find in Library

Herein, we describe the development of one-pot transformation of α-ethoxy derivatives of phosphorus analogs of protein and non-protein α-amino acids into biologically important <i>N</i>-protected 1-aminobisphosphonates. The proposed strategy, based on the three-component reaction of 1-(<i>N</i>-acylamino)-1-ethoxyphosphonates with triphenylphosphonium tetrafluoroborate and triethyl phosphite, facilitates good to excellent yields under mild reaction conditions. The course of the reaction was monitored by ³¹P NMR spectroscopy, allowing the identification of probable intermediate species, thus making it possible to propose a reaction mechanism. In most cases, there is no need to use a catalyst to provide transformation efficiency, which increases its attractiveness both in economic and ecological terms. Furthermore, we demonstrate that the one-pot procedure can be successfully applied for the synthesis of structurally diverse <i>N</i>-protected bisphosphonic analogs of α-amino acids. As shown, the indirect formation of the corresponding phosphonium salt as a reactive intermediate during the conversion of 1-(<i>N</i>-acylamino)-1-ethoxyphosphonate into a 1-aminobisphosphonate derivative is a crucial component of the developed methodology.