Synergistic Catalysis between a Dipeptide Phosphonium Salt and a Metal‐Based Lewis Acid for Asymmetric Synthesis of N‐Bridged [3.2.1] Ring Systems

We present an unprecedented synergic catalytic route for the asymmetric construction of fluorinated N‐bridged [3.2.1] cyclic members of tropane family via a bifunctional phosphonium salt/silver co‐catalyzed cyclization process. A broad variety of substrates bearing an assortment of functional groups...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2022-09, Vol.61 (38), p.e202207334-n/a
Main Authors: Chen, Yuan, He, Jiajia, Zhuang, Cheng, Liu, Zanjiao, Xiao, Kai, Su, Zhishan, Ren, Xiaoyu, Wang, Tianli
Format: Article
Language:English
Subjects:
Asymmetric synthesis
Asymmetry
Catalysis
Chemical synthesis
Computer applications
Cooperative Catalysis
Functional groups
Lewis acid
Lewis Acids
N-Bridged [3.2.1] Rings
Phosphonium Salts
Reaction Mechanisms
Silver
Substrates
Tropane
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Summary:We present an unprecedented synergic catalytic route for the asymmetric construction of fluorinated N‐bridged [3.2.1] cyclic members of tropane family via a bifunctional phosphonium salt/silver co‐catalyzed cyclization process. A broad variety of substrates bearing an assortment of functional groups are compatible with this method, providing targeted compounds bearing seven‐membered ring and four contiguous stereocenters in high yields with excellent stereoselectivities. The gram‐scale preparations, facile elaborations and preliminary biological activities of the products demonstrate the application potential. Moreover, both experimental and computational mechanistic studies revealed that the cyclization proceeded via a “sandwich” reaction model with multiple weak‐bond cooperative activations. Insights gained from our studies are expected to advance general efforts towards the catalytic synthesis of challenging chiral heterocyclic molecules. A synergic catalytic method for asymmetric construction of N‐bridged [3.2.1] rings by a phosphonium salt/silver co‐catalyzed cyclization has been developed. This route affords fluorine‐installed tropane derivatives in excellent stereoselectivities. The mechanistic results revealed that the silver nitrite was installed on the phosphonium salt via hydrogen bonding and simultaneously activated the dipole, in a “sandwich” reaction model.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202207334