Synthesis of Chiral α-Substituted β-Carboxyethylphosphonic Acids by Palladium-Catalyzed Hydroesterification

Abstract

An efficient palladium-catalyzed asymmetric hydroesterification of alkenylphosphonic acids has been developed to access chiral α-substituted β-carboxyethylphosphonic acids. This atom-economical transformation employs a palladium catalyst combined with WingPhos, a rigid P-stereogenic bidentate phosphine ligand, enabling one-step construction of structurally diverse chiral phosphonic acids. The mechanistic studies demonstrate that the phosphonic acid moiety is critical for promoting the overall reactivity. A synergistic interplay between the substrate’s internal acidic protons and an external Brønsted acid accelerating the generation of catalytically active palladium hydride species was revealed.