47. C–H Acidity and Arene Nucleophilicity as Orthogonal Control of Chemoselectivity in Dual C–H Bond Activation

Liu, J.-R.; Duan, Y.-Q.; Zhang, S.-Q.; Zhu, L.-J.; Jiang, Y.-Y.;* Bi, S.;* Hong, X.* Org. Lett., 2019, 21, 2360–2364. Download Link

Abstract: We discovered a cooperative gold/silver catalysis mechanism in the oxidative cross-coupling reaction between 1,2,4,5-tetrafluorobenzene and N-TIPS-indole, using DFT calculations. A silver(I)- catalyzed CMD mechanism is responsible for the C−H activation of 1,2,4,5-tetrafluorobenzene, and C−H acidity determines the chemoselectivity. A gold(III)-catalyzed SE2Ar mechanism is responsible for the C3−H activation of N-TIPS-indole, and arene nucleophilicity determines the chemo- and regioselectivity. The orthogonal chemoselectivity control provides a mechanistic guide for dual C−H activation reactions.