Synthesis of Fused Polycyclic Indole-Indenone Scaffolds via Pd-Catalyzed Sequential Cycloaddition Reactions

A Pd-catalyzed Sonogashira coupling of iodoalkynones with propargylic ethers bearing indole-tethered unactivated alkenes, followed by an Alder-ene reaction and a Diels-Alder cycloaddition, provides access to various hexacyclic heterocycles containing a dihydropyrido[1,2-a]indole scaffold. When similar N-propargylic allylic ethers were applied to the reaction, polycyclic compounds containing pyrido[1,2-a]indole scaffolds could be obtained after treatment of the fused cyclic products with trifluoroacetic acid. The method features a broad substrate scope, high stereoselectivity, and mild reaction conditions.