Regioselective Palladium-Catalyzed C‑H Bond Trifluoroethylation of Indoles: Exploration and Mechanistic Insight
journal contributionposted on 29.01.2018, 00:00 by Hao Zhang, Hao-Yang Wang, Yixin Luo, Chaohuang Chen, Yimiao Cao, Pinhong Chen, Yin-Long Guo, Yu Lan, Guosheng Liu
A selective palladium-catalyzed trifluoroethylation reaction of indoles has been developed. The C-H bond activation process, using CF3CH2I as the fluoroalkyl source, can be employed to prepare a variety of 2-CF3CH2 substituted indoles. Moreover, because it displays a wide functional group tolerance, the process can be employed to synthesize CF3CH2-containing bioactive indoles through late-stage trifluoroethylation. The results of a preliminary mechanistic study and DFT calculations show that a β-diketone, acting as an ionic palladium ligand, plays an important role in governing the efficiency of the palladium-catalyzed trifluoroethylation reaction by accelerating the oxidative addition step. In contrast, transfer of the indole N-H proton in the palladium center is involved in the rate-determining step.
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β- diketoneC-H bond activation processDFT calculations showbioactive indolesindole N-H protongroup tolerancefluoroalkyl sourceCF 3 CH 2oxidative addition steppalladium ligandpalladium centerrate-determining steppalladium-catalyzed trifluoroethylation reactionlate-stage trifluoroethylationMechanistic Insight2- CF 3 CH 2