Non-symmetrical Bisphosphonated allylic amines: unprecedented synthesis from α-aminomonophosphonates

Abstract

Interest in the synthetic routes to aminobisphosphonates has been steadily increasing due to their wide range of applications. In this work, we report a novel approach for the preparation of two series of non-symmetric allylic aminobisphosphonates under mild reaction conditions. The target compounds were obtained via nucleophilic substitution of α-aminophosphonates with two different phosphonated bromine derivatives: 2-bromoethyl diethyl phosphonate and ethyl 2-(bromomethyl)-3-(diethoxyphosphoryl)acrylate. In the case of N-(phosphorylmethyl)-N-(2-phosphorylethyl) allylamines, the allyl fragment originates from allyl-substituted α-aminophosphonates, whereas for N-(phosphorylmethyl)-3-phosphorylallylamine, it is introduced through the ethyl 2-(bromomethyl)-3-(diethoxyphosphoryl)acrylate synthon.