Ruthenium(II)-Carboxylate-Catalyzed C4/C6–H Dual Alkylations of Indoles

Abstract Position-selective functionalizations of specific C–H bonds are in high demand. Especially, the selectivity beyond the traditional C2- and C3-manifold is highly challenging. Herein, we disclose site-selective C4/C6–H double alkylations of indoles accomplished by arene-ligand-free ruthenium(II)-carboxylate catalysis. Base-assisted C2–H ruthenation enabled the C4/C6–H dialkylations with ample substrate scope. The robust C4/C6–H alkylations were demonstrated by gram-scale syntheses and late-stage diversifications. Mechanistic studies unraveled the unique features of ruthenium(II)-catalyzed C4/C6–H indole functionalizations.