Synthesis of Anti-Inflammatory α-Arylalkanoic Acids by 1,2-Aryl Shift. New Synthetic Methods (42)

α-Arylalkanoic acids have acquired importance as anti-inflammatory agents and are now in great demand on the pharmaceutical front. Hence, the need has arisen for new and improved, economical synthetic procedures suitable for their preparation and manufacture on an industrial scale. For many years the synthetic approach to this class of compounds was restricted to the Willgerodt and Darzen reactions. More recently, several methods have been developed which are based on the 1,2-aryl shift in acetals of α-functionalized alkyl aryl ketones. This new approach starts from the oxythallation of alkyl aryl ketones first described by Taylor and McKillop in 1971. Asymmetric syntheses of some important arylakanoic acids have also been developed on this basis. The highly toxic thallium salts may be replaced, inter alia, by catalytically effective metal salts.