Modular One‐Step Three‐Component Synthesis of Tetrahydroisoquinolines Using a Catellani Strategy

Reported is a modular one‐step three‐component synthesis of tetrahydroisoquinolines using a Catellani strategy. This process exploits aziridines as the alkylating reagents, through palladium/norbornene cooperative catalysis, to enable a Catellani/Heck/aza‐Michael addition cascade. This mild, chemose...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2018-08, Vol.57 (34), p.10980-10984
Main Authors: Qian, Guangyin, Bai, Miao, Gao, Shijun, Chen, Han, Zhou, Siwei, Cheng, Hong‐Gang, Yan, Wei, Zhou, Qianghui
Format: Article
Language:English
Subjects:
Alkylation
Aromatic compounds
Atom economy
aziridines
Catalysis
Catellani reaction
cooperative catalysis
heterocycles
Palladium
Reagents
Regioselectivity
Stereoselectivity
Substitutes
Substrates
Synthesis
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Summary:Reported is a modular one‐step three‐component synthesis of tetrahydroisoquinolines using a Catellani strategy. This process exploits aziridines as the alkylating reagents, through palladium/norbornene cooperative catalysis, to enable a Catellani/Heck/aza‐Michael addition cascade. This mild, chemoselective, and scalable protocol has broad substrate scope (43 examples, up to 90 % yield). The most striking feature of this protocol is the excellent regioselectivity and diastereoselectivity observed for 2‐alkyl‐ and 2‐aryl‐substituted aziridines to access 1,3‐cis‐substituted and 1,4‐cis‐substituted tetrahydroisoquinolines, respectively. Moreover, this is a versatile process with high step and atom economy. A modular synthesis of tetrahydroisoquinolines was developed. Aziridines act as the alkylating reagents to enable a Catellani/Heck/aza‐Michael addition cascade by palladium/norbornene (NBE) cooperative catalysis. This mild, chemoselective, and scalable protocol is compatible with a wide range of readily available aryl iodides, aziridines, and olefins. Excellent regio‐ and diastereoselectivities are observed for 1,3‐cis‐substituted and 1,4‐cis‐substituted tetrahydroisoquinolines.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201806780