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

Authors: Longwu Ye ,Tong-De Tan, Xin-Qi Zhu,  Hao-Zhen Bu,  Guocheng Deng,  Yang-Bo Chen,  Rai-Shung Liu

Abstract:

Catalytic cycloisomerization‐initiated cascade cyclizations of terminal alkynes have received tremendous interest, and been widely used in the facile synthesis of a diverse array of valuable complex heterocycles. However, these tandem reactions have been mostly limited to noble‐metal catalysis, and initiated via an exo‐cyclization pathway. Reported herein is an unprecedented copper‐catalyzed endo‐cyclization‐initiated tandem reaction of indolyl homopropargyl amides, where copper catalyzes both the hydroamination and Friedel−Crafts alkylation process. This method allows the practical and atom‐economical synthesis of valuable bridged aza‐[n.2.1] skeletons (n = 3–6) with wide substrate scope, and excellent diastereoselectivity and enantioselectivity by a chirality‐transfer strategy. Moreover, the mechanistic rationale for this novel cascade cyclization is also strongly supported by control experiments, which is distinctively different from the related gold catalysis.

Full-Link: https://onlinelibrary.wiley.com/doi/10.1002/anie.201904698