Syntheses of SGLT2 Inhibitors by Ni- and Pd-Catalyzed Fukuyama Coupling Reactions

Nickel- and palladium-catalyzed Fukuyama coupling reactions of a d-gluconolactone-derived thioester with arylzinc reagents at ambient temperature provided the corresponding multifunctional aryl ketones in high yield. Ligand screening for the nickel-catalyzed Fukuyama coupling reactions indicated that 1,2-bis­(dicyclohexylphosphino)­ethane (dCype) served as a superior supporting ligand to improve the product yield. In addition, Pd/C was a practical alternative that enabled ligand-free Fukuyama coupling reactions and was efficiently applied to the key C–C bond-forming step to prepare canagliflozin and dapagliflozin, which are diabetic SGLT2 inhibitors of current interest.