An Efficient and Versatile Synthesis of Isoflavones from 2-Methoxybenzoic Acids

Isoflavones (3-aryl-4H-1-benzopyran-4-ones) are found naturally in soybeans and many plants of the Leguminosae family. They have attracted much attention due to their biological activities, such as their anti-cancer, anti-inflammatory, and antifungal properties. Isoflavones intake through foods is important to human health, because they potentially regulate fatty acid metabolism and methoxy-substituted isoflavones in particular increase cell permeability. Isoflavones have also been synthesized by the coupling of 3-iodochromones with arylboronic acids. The condensation of 2'-hydroxyacetophenones with DMF dimethyl acetal formed 3-(dimethylamino)-2'-hydroxyphenylpropenones, which were cyclized using iodine to form 3-iodochromones. This process was followed by Suzuki coupling with arylboronic acids or aryl boronates to obtain isoflavones. The synthesis of isoflavones (6) from 5 was based on the formylation of the methylene group of 5 using DMF-POCl₃. Previously, the reaction of the DMF-POCl₃ complex on benzyl 2-hydroxyphenyl ketones led to isoflavones, for which DMF was used as the reagent and solvent for 18 h at gentle reflux