A palladium-catalyzed cascade double annulation reaction to access unsymmetrical di(heteroaryl)methanes.

A palladium-catalyzed cascade double annulation reaction for the synthesis of unsymmetrical di(heteroaryl)methanes from non-heteroaryl substrates has been developed. This five-step cascade reaction integrates a furan ring and an indole/isoquinolinone scaffold into a methane molecule through η3-allylpalladium(II)-catalyzed cycloisomerization of β-chlorovinyl ketones followed by allylic heteroarylation, enabling the rapid construction of diverse heteroaryl units with a flexible methylene linker. Furthermore, initial screening indicated that compound 5fa exhibited potential antitumor activity in HeLa cells with the highest inhibition rate among the selected compounds.