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Expedient Synthesis of Bridged Bicyclic Nitrogen Scaffolds via Orthogonal Tandem Catalysis
Author(s) -
Biswas Sovan,
Van Steijvoort Ben F.,
Waeterschoot Marjo,
Bheemireddy Narendraprasad Reddy,
Evano Gwilherm,
Maes Bert U. W.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202106716
Subject(s) - catalysis , chemistry , tandem , intramolecular force , bicyclic molecule , combinatorial chemistry , enamine , stereochemistry , organic chemistry , materials science , composite material
Bridged nitrogen bicyclic skeletons have been accessed via unprecedented site‐ and diastereoselective orthogonal tandem catalysis from readily accessible reactants in a step economic manner. Directed Pd‐catalyzed γ‐C(sp 3 )‐H olefination of aminocyclohexane with gem‐dibromoalkenes, followed by a consecutive intramolecular Cu‐catalyzed amidation of the 1‐bromo‐1‐alkenylated product delivers the interesting normorphan skeleton. The tandem protocol can be applied on substituted aminocyclohexanes and aminoheterocycles, easily providing access to the corresponding substituted, aza‐ and oxa‐analogues. The Cu catalyst of the Ullmann‐Goldberg reaction additionally avoids off‐cycle Pd catalyst scavenging by alkenylated reaction product. The picolinamide directing group stabilizes the enamine of the 7‐alkylidenenormorphan, allowing further product post functionalizations. Without Cu catalyst, regio‐ and diastereoselective Pd‐catalyzed γ‐C(sp 3 )‐H olefination is achieved.