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

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 S_E2Ar 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.