An Improved Iodine-Catalyzed Aromatization Reaction and Its Application in the Synthesis of a Key Intermediate of Cannabidiol

Abstract

In this study, the development of an improved process for the synthesis of a key cannabidiol intermediate, methyl olivetolate, is described. The process involves an improvement of the iodine-catalyzed aromatization of cyclohexanone using potassium persulfate as an oxidant. This approach enabled for the efficient synthesis of methyl olivetolate with a 90% yield and 99.84% HPLC purity on a 5 kg scale. Additionally, a total of 16 cyclohexanone substrates afforded higher yields (75-92%) of m-diphenol compounds compared to the established methods.