Stereoselective Construction of Unsymmetrically Linked Heterocycles via Palladium-Catalyzed Alkyne Insertion/Cycloimidoylation Cascade

Abstract

A novel strategy to access unsymmetrically linked heterocycles via palladium-catalyzed acylcycloimidoylation of alkyne-tethered carbamoyl chlorides with isocyanides has been developed. Functionalized isocyanides were successfully applied as imine-containing heterocycle precursors to capture the vinyl-PdII intermediate, which was generated from a syn-carbopalladation of alkyne, followed by subsequent intramolecular C–H bond activation/imidoylative Heck reactions. Methylene oxindoles within Z-tetrasubstituted olefins were obtained in high yields with excellent stereoselectivities. Broad functional groups were well tolerated under mild reaction conditions.

Synthesis of Bis-Heterocycles Bearing Methyleneindole Motifs by Pd-Catalyzed Domino Reaction

“…As we know, embedding two or more heterocyclic scaffolds with intrinsic bioactivities into a single agent may result in a hybridized molecule with dual-activity . However, generating more complex heterocyclic scaffolds via introducing another heterocycle to the methylene oxindole moiety is yet to be studied …”