Photoredox/Nickel Dual Catalysis-Enabled Modular Synthesis of Arylallyl Alcohols with Acetylene as the Two-Carbon Synthon

Arylallyl alcohols are commonly found
in natural products and drug
molecules. The traditional syntheses primarily rely on two-component
reactions using presynthesized alkenes. Herein, we report a photoredox/nickel
dual-catalyzed three-component cross-coupling reaction, which enables
the rapid synthesis of arylallyl alcohols with acetylene as a two-carbon
(C2) synthon. In this reaction, the aryl halide and carbonyl compound
were sewn together with acetylene as the linker. A series of arylallyl
alcohols were synthesized in an acetylene atmosphere (1 atm). This
method features broad substrate scopes, good functional group tolerance,
and high Z-selectivity. In addition to the intermolecular
difunctionalization of acetylene, the reaction is also amenable to
intramolecular ring formation, giving highly valuable indenols and
indanones. The mechanistic investigation indicates that the alkenylnickel
is the key intermediate. This intermediate can be considered as an
alternative alkenyl Grignard reagent but with better functional group
compatibility. With this method as the key step, several important
molecules including natural products and drug molecules have been
prepared.