Scope and Mechanism of the Ruthenium-Catalyzed sp³ C–H Coupling Reaction of 2-Alkylindoles with Enones for the Synthesis of Carbazole Derivatives

The catalytic system consisting of a cationic Ru–H complex 1 and 3,4,5,6-tetrachloro-1,2-benzoquinone (L1) was found to be highly effective for the dehydrative sp3 C–H coupling reaction of 2-alkyl substituted indoles with enones to form 2,4-disubstituted carbazole products. The analogous coupling reaction of 2-alkylindoles with linear enones bearing the cyclic olefinic group afforded tetracyclic carbazole products. A normal deuterium kinetic isotope effect was measured from the coupling reaction of 1,2-dimethylindole versus 1-methyl-2-(methyl-d3)indole with (E)-3-penten-2-one (kH/kD = 2.5). The Hammett plot was constructed from the reaction of para-substituted indoles 5-X-1,2-dimethylindole (X = OMe, Me, H, F, and Cl) with 4-phenyl-3-buten-2-one (ρ = −1.6 ± 0.2). The density functional theory (DFT) calculations were performed to obtain a complete energy profile for the coupling reaction. The combined experimental and DFT computational data revealed a detailed mechanistic path that features an initial coupling of indole and enone substrates, the turnover-limiting heterolytic sp3 C–H activation step, and the subsequent cyclization and dehydration steps. The catalytic method provides an efficient synthesis of carbazole derivatives from the dehydrative sp3 C–H coupling reaction of readily available indole with enone substrates without employing any reactive reagents or forming wasteful byproducts.