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

Abstract

NHCHO P(O)(OMe)2 X CHN2 X = Br -N2 -HC(O)NH2 X = P(O)(OEt)2 R = P(O)(OEt)2, 4-(EtO)2P(O)-C6H4, trans-(EtO)2P(O)-CH=CH NHCHO P(O)(OMe)2 NHCHO P(O)(OMe)2 Pd catalysis HN N P(O)(OMe)2 (EtO)2(O)P Br RAbstract 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.