Synthesis of 1,1-bis(indolyl)alkenes via nickel-catalyzed selective alkynylation of indoles with haloalkynes

Abstract

Herein, we present a mild and efficient method for the synthesis of 1,1-bis(indolyl)alkenes via nickel-catalyzed cascade alkynylation and Friedel–Crafts 3-alkenylation of indoles with haloalkynes. This strategy employs readily available starting materials and exhibits excellent substrate generality. The practicality of this strategy was further proved by a gram-scale reaction and late-stage modifications, demonstrating potential applications in medicinal chemistry and functional materials. Mechanistic studies indicate that 3-alkynylindole is the key intermediate, and HFIP serves as a critical solvent that facilitates both C–H activation and nucleophilic addition in this chemical process.