Copper‐Catalyzed Cascade Cyclization of Indolyl Homopropargyl Amides: Stereospecific Construction of Bridged Aza‐[n.2.1] Skeletons

Abstract

Catalytic cycloisomerization-initiated cascade cyclizations of terminal alkynes have received tremendous interest, and been widely used in the facile synthesis of adiverse arrayof valuable complex heterocycles.H owever,t hese tandem reactions have been mostly limited to noble-metal catalysis,and are initiated by an exo-cyclization pathway. Reported herein is an unprecedented copper-catalyzed endo-cyclization-initiated tandem reaction of indolyl homopropargyl amides,w here copper catalyzesb oth the hydroamination and Friedel-Crafts alkylation process.This method allows the practical and atomeconomical synthesis of valuable bridged aza-[n.2.1] skeletons (n = 3-6) with wide substrate scope,and excellent diastereoselectivity and enantioselectivity by ac hirality-transfer strategy. Moreover,t he mechanistic rationale for this novel cascade cyclization is also strongly supported by control experiments, and is distinctively different from the related gold catalysis.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Extended Multicomponent Reactions with Indole Aldehydes: Access to Unprecedented Polyheterocyclic Scaffolds, Ligands of the Aryl Hydrocarbon Receptor

“…Indoles are common scaffolds in drugs and bioactive compounds. Furthermore, they are influential motifs in the design of domino processes [10][11][12] and indole carbaldehydes have already displayed a rich reactivity in this endeavor. [13][14][15] Indoles are also present in a variety of MCRs.…”