Palladium-Catalyzed Reaction of Aryl Iodides and Glycal Enones: Application in the Preparation of Dapagliflozin Analogues

Abstract

An efficient approach for the preparation of C-1 aryl enones from aryl iodides and glycal enones by palladium-catalyzed cross-coupling reactions under ligand-free conditions was developed. A wide range of aryl iodides bearing electron-donating and withdrawing groups underwent oxidative C-1 arylation with galactal, glucal and rhamnal enones in the presence of Pd(OAc)2 and AgNO3 under mild conditions. The protecting groups, including benzyl, acetyl, pivaloyl, and benzoyl groups, were found to be compatible under standard reaction conditions. The developed methodology was applied for the preparation of dapagliflozin analogues (SGLT-2 inhibitors). Regioselective nitration of C-1 aryl enones provides C-2 nitro aryl enones in good yields. © 2022 Wiley-VCH GmbH.