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.

Automated summary

In this study, a photoredox/nickel dual-catalyzed three-component cross-coupling reaction was reported for the rapid synthesis of arylallyl alcohols using acetylene as a linker. This method exhibited broad substrate scopes, good functional group tolerance, and high Z-selectivity, and it could be applied for intramolecular ring formation to obtain valuable indenols and indanones.