Palladium-Catalyzed Synthesis of Aryl phosphonates Using Sodium Hypophosphite

Abstract

Aryl phosphonates represent a class of crucial structural motifs widely embedded in pharmaceutical molecular frameworks. Conventional synthetic approaches typically rely on PCl₃ or P(O)Cl₃ as the phosphorus source, which face two major challenges: the inherent toxicity and instability of the phosphorus reagents, and the harsh reaction conditions accompanied by tedious operational procedures. There is an increasing need for alternative phosphorus sources that are more stable, greener, and cost-effective to replace the commonly used PCl₃. Here in, we disclose a facile and efficient method for synthesizing aryl phosphonates from alcohol reagents and aryl halides, using stable, green, and readily available NaH2PO2 as a phosphorus source in a one-pot, multicomponent fashion that proceeds under very mild conditions for the first time. Notably, this approach not only eliminates the use of PCl₃ but also enhances both the synthetic efficiency and practical applicability of aryl phosphonates significantly.