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.