Synthesis of 2-Arylpropionic Acids by Pd-Catalyzed Carbonylation of Vinylarenes in the Presence of Formic Acid under Mild Conditions

Abstract

An efficient synthesis of valuable 2-arylpropanoic acids by Pd-catalyzed carbonylation of the corresponding alkenes with CO and formic acid is described. High regioselectivity is achieved by the addition of polyvinylpyrrolidone. The advantages of the proposed method include mild reaction conditions, an accessible catalytic system, and low Pd loading. The target 2-arylpropanoic acids were obtained in yields ranging from 48 to 77%. The method was applied in the total synthesis of rac-naproxen starting from commercially available 6-hydroxy-2-naphthoic acid. The hydroxycarbonylation of vinyl acetate to produce 2-acetoxypropanoic acid is also demonstrated.