Exploiting Palladium-Catalyzed Cross-Coupling for the Synthesis of 2-Aryl-Substituted 1-Aminocyclopropylphosphonates

A series of 2-aryl-substituted 1-aminocyclopropylphosphonates containing an additional remote phosphonate group have been synthesized starting from readily accessible dimethyl (1R*,2R*)-2-(4-bromophenyl)-1-formamidocyclopropylphosphonate using cross-coupling methodology. Different types of palladium-catalyzed reactions for carbon-carbon and carbon-phosphorus bond formation were realized. In each case the optimum conditions were found to obtain the desired products in high yield in both small- and large-scale experiments.