Regiodivergent C–H Alkylation of Quinolines with Alkenes by Half-Sandwich Rare-Earth Catalysts

The regiodivergent catalysis of C–H alkylation with alkenes is of great interest and importance but has remained hardly explored to date. We report herein the first regiodivergent C–H alkylation of quinolines with alkenes by half-sandwich rare-earth catalysts. The regiodivergence was achieved by fine-tuning the metal/ligand combination or steric and electronic properties of the catalysts. The use of the C5Me5-ligated scandium catalyst Sc-3 for the reaction of quinolines with styrenes and that of the C5Me4H-ligated yttrium catalyst Y-2 for the reaction with aliphatic olefins exclusively afforded the corresponding C8–H alkylation products, thus constituting the first example of direct C8–H alkylation of neutral quinolines. In contrast, the Sc-3-catalyzed reaction of 2-arylquinolines with aliphatic olefins and the Y-2-catalyzed reaction with styrenes selectively gave the 2-aryl o-C–H alkylation products. On the basis of the catalyst/substrate-controlled regiodivergence, the sequential regiospecific dialkylation of quinolines with two different alkenes has also been achieved. DFT studies revealed that the C–H activation of 2-phenylquinoline at both the C8 position and an ortho position of the 2-phenyl substituent was possible, and these two types of initially formed C–H activation products were interconvertible through the coordination and C–H activation of another molecule of quinoline. The regioselectivity for the C–H alkylation reactions was governed not only by the ease of the initial formation of the C–H activation products but also by the energy barriers for their interconversions, as well as by the energy barriers or steric and electronic influences in the subsequent alkene insertion processes. This work has not only constituted an efficient protocol for the selective synthesis of diversified quinoline derivatives but also offered unprecedented insights into the C–H activation and transformation of quinolines and may help in the design of more efficient, selective, or complementary catalysts.