Concise Synthesis of Chiral Tricyclic Lactams by Tandem Dynamic Kinetic Asymmetric Reductive Amination/Lactamization Using Ammonium Salts

The atom‐ and step‐efficient synthesis of chiral fused tricyclic lactams from readily available ketoesters using cheap ammonium salts as the nitrogen source is reported. This ruthenium‐catalyzed system operates through an efficient tandem dynamic kinetic asymmetric reductive amination (ARA)/lactamiz...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2023-06, Vol.62 (25), p.e202303868-n/a
Main Authors: Wang, Jingxin, Shi, Yongjie, Wang, Fangyuan, Huang, Fanping, Bai, Shao‐Tao, Zhao, Yu, Zhang, Xumu
Format: Article
Language:English
Subjects:
Amination
Ammonium
Ammonium Compounds
Ammonium salts
Asymmetry
Catalysis
Catalysts
Dynamic Kinetic Asymmetric Transformation
Enantiomers
Enantioselectivity
Intermediates
Ketoesters
Lactamization
Lactams
Polycyclic Lactams
Reductive Amination
Rivastigmine
Ruthenium
Salts
Synthesis
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Summary:The atom‐ and step‐efficient synthesis of chiral fused tricyclic lactams from readily available ketoesters using cheap ammonium salts as the nitrogen source is reported. This ruthenium‐catalyzed system operates through an efficient tandem dynamic kinetic asymmetric reductive amination (ARA)/lactamization and produces chiral fused tricyclic lactams in high yields with excellent diastereo‐ and enantioselectivity (up to >99 % ee, >20 : 1 dr and 98 % yield). The robust method was also applied to the concise synthesis of key intermediates in the synthesis of rivastigmine analogues and chiral N‐heterocyclic carbene catalysts. An efficient and economical one‐pot approach to chiral fused tricyclic lactams from readily available ketoesters was developed by using cheap ammonium salts as the nitrogen source through ruthenium‐catalyzed tandem dynamic kinetic asymmetric reductive amination/lactamization. This protocol provides highly efficient access to drug intermediates and organocatalysts containing chiral polycyclic N‐heterocycles.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202303868