Copper-Catalyzed Formal [4 + 1] Annulation of Diynes with Isoxazoles: Synthesis of Pyrrolo[3,4-b]indoles

Catalytic annulation of isoxazoles with alkynes is an efficient methodology for the assembly of N-heterocyclic architectures, and most reactions require noble-metal catalysts. Herein, we disclose a copper-catalyzed formal [4 + 1] annulation of 1,6-diynes with isoxazoles for the efficient and atom-economical construction of biologically important pyrrolo[3,4-b]indoles in high yields via vinyl cation intermediates, which is significantly different from previous annulations of alkynes with isoxazoles involving α-imino metal carbene intermediates. Interestingly, preliminary results have been obtained for the related catalytic atroposelective transformation. Computational mechanistic studies are employed to elucidate the reaction mechanism.