Palladium-catalyzed difluoromethylcarbonylation of aryl iodides

Abstract

We report a palladium-catalyzed carbonylative difluoromethylation of aryl iodides with (DMPU)₂Zn(CF₂H)₂ under CO, providing direct one-pot access to aryl difluoromethyl ketones (DFMKs). Using a Pd(PPh₃)₄/RuPhos system in DMSO/DMF, a wide range of electron-neutral and electron-rich aryl iodides are efficiently transformed into the corresponding DFMKs. The resulting ketones readily undergo a range of downstream transformations, including Wittig olefination, hydrogenation, cyclization, and reduction. The utility of this methodology is demonstrated through the late-stage modification of pharmacologically important intermediates, such as an AgAChE inhibitor precursor. This scalable and practical protocol offers a versatile route to DFMKs for medicinal chemistry and complex molecule synthesis.