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Angew Chem Int Ed Engl. 2019 May 16. doi: 10.1002/anie.201904698. [Epub ahead of print]

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

Author information

1
State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
2
Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan.
3
State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, China.

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.

KEYWORDS:

copper; cyclizations; heterocycles; stereoselectivity; synthetic methods

PMID:
31095848
DOI:
10.1002/anie.201904698

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