Direct ortho‐Trifluoroethylation of Aromatic Ureas by Palladium Catalyzed C‐H activation: A Missing Piece of Aromatic Substitutions

Abstract

Development of direct late-stage installation of key fluorinated functional groups into aromatic systems is an important and challenging task of current organic chemistry. Herein, we report a novel palladium catalyzed trifluoroethylation process by C-H activation for the access of ortho trifluoroethylated aromatic ureas. The application of novel, highly active trifluoroethyl(mesityl)iodonium salt enables the efficient introduction of the trifluoroethyl group at 25 °C in 3 hours in high yields (up to 95%) with good functional group tolerance. Abstract: Development of direct late-stage installation of key fluorinated functional groups into aromatic systems is an important and challenging task of current organic chemistry. Herein, we report a novel palladium catalyzed

Design of Trifluoroalkenyl Iodonium Salts for a Hypervalency‐Aided Alkenylation–Cyclization Strategy: Metal‐Free Construction of Aziridine Rings

“…Scheme shows the free energy profile of the route leading to the formation of the aziridine ring in a simple model reaction of aniline and 2 e . In agreement with earlier findings, we found that the resting state of the iodonium salt corresponds to its dissociated form ,. The reaction is initiated by a weak C−N interaction between the iodonium cation and the amine.…”

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…The same group reported also an ortho -trifluoroethylation reaction of N -arylureas, where they basically applied a protocol they had previously used for the same transformation with amide substrates ( Scheme 24G ) and obtained excellent yields ( Scheme 43B ). 263 …”

Progress on Trifluoroethylation Reactions Using Aryl(trifluoroethyl)iodonium Salts

“…In a similar manner, Novák and coworkers developed a palladium-catalyzed trifluoroethylation process for the preparation of ortho-trifluoroethyl aromatic ureas through C -H activation (Scheme 22). [24] The use of [Me-sICH 2 CF 3 ][OTf] as a CH 2 CF 3 transfer source allowed the efficient and selective introduction of the trifluoroethyl group at 25 ℃. 2,2,2-Trifluoroacetic acid (TFA) significantly improved the formation of the desired products.…”

“…The DFT calculations suggested that the rate determining oxidative CH 2 CF 3 transfer step was preceded by an unexpected C-H activation route on the Pd center during the catalytic cycle, where the deprotonation was assisted by an external triflate anion. [24] The formation of bimetallic palladium species is a crucial step of the reaction, which has an important role in the mild catalytic transformation. This reaction accomplished direct and late-stage trifluoroethylation of urea derivatives with good yields, high efficiency, and excellent functional group tolerance under mild conditions.…”

“…This reaction accomplished direct and late-stage trifluoroethylation of urea derivatives with good yields, high efficiency, and excellent functional group tolerance under mild conditions. [24] Scheme 22 Pd-catalyzed trifluoroethylation of aromatic ureas by [MesICH 2 CF 3 ][OTf]…”