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Copper‐Catalyzed Cascade Cyclization of Indolyl Homopropargyl Amides: Stereospecific Construction of Bridged Aza‐[ n .2.1] Skeletons
Author(s) -
Tan TongDe,
Zhu XinQi,
Bu HaoZhen,
Deng Guocheng,
Chen YangBo,
Liu RaiShung,
Ye LongWu
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201904698
Subject(s) - hydroamination , catalysis , cycloisomerization , chemistry , cascade reaction , combinatorial chemistry , tandem , copper , alkylation , cascade , atom economy , stereospecificity , substrate (aquarium) , stereochemistry , organic chemistry , materials science , composite material , oceanography , chromatography , geology
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.