Copper‐Catalyzed Cascade Cyclization of Indolyl Homopropargyl Amides: Stereospecific Construction of Bridged Aza‐[n.2.1] Skeletons. (6th June 2019)

• Record Type: Journal Article
• Authors: Tan, Tong‐De; Zhu, Xin‐Qi; Bu, Hao‐Zhen; Deng, Guocheng; Chen, Yang‐Bo; Liu, Rai‐Shung; Ye, Long‐Wu
• Is Part Of: Angewandte Chemie. Volume 131:Number 28(2019)
• Page Start: 9734
• Page End: 9741
• Publication Date: 2019-06-06
• Subjects: Cyclisierungen -- Heterocyclen -- Kupfer -- Stereoselektivität -- Synthesemethoden; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201904698
• Languages: English
• ISSNs: 0044-8249

Abstract

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 are initiated by 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, and is distinctively different from the related gold catalysis. Abstract : Eine Cu‐katalysierte endo ‐Cyclisierung induziert die Tandemreaktion von Indolylhomopropargylamiden, wobei Kupfer sowohl die Hydroaminierung als auch den Friedel‐Crafts‐Alkylierungsprozess katalysiert. Die Anti‐Markownikow‐Addition übertrumpft die typische Markownikow‐Addition, und die Methode ermöglicht die atomökonomische Synthese verbrückter Aza‐[ n .2.1]‐Gerüste ( n =3–6) mit ausgezeichneter Diastereo‐ und Enantioselektivität.