Cationic Foldamer‐Catalyzed Asymmetric Synthesis of Inherently Chiral Cages

• Published in: Angewandte Chemie International Edition 2024-11, Vol.63 (46), p.e202411889-n/a
• Main Authors: Fang, Siqiang, Bao, Zhaowei, Liu, Zanjiao, Wu, Zhengdong, Tan, Jian‐Ping, Wei, Xin, Li, Bo, Wang, Tianli
• Format: Article
• Language: English
• Subjects: Asymmetric Synthesis; Asymmetry; Cage molecules; Cationic Foldamer Catalysis; Chemical reactions; Chemical synthesis; Ethers; Inherently Chiral Cages; Prisms; Remote Desymmetrization; SNAr Reaction; Stereochemistry
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202411889

The stereochemistry of shape‐persistent molecular cages, particularly those resembling prisms, exerts significant influence on their application‐specific functionalities. Although methods exist for fabricating inherently chiral prism‐like cages, strategies for catalytic asymmetric synthesis of these structures in a diversity‐oriented fashion remain unexplored. Herein, we introduce an unprecedented organocatalytic desymmetrization approach for the generation of inherently chiral prism‐like cages via phosphonium‐containing foldamer‐catalyzed SNAr reactions. This methodology establishes a topological connection, enabling the facile assembly of a wide range of versatile stereogenic‐at‐cage building blocks possessing two highly modifiable groups. Furthermore, subsequent stereospecific transformations of the remaining chlorides and/or ethers afford convenient access to numerous functionally relevant chiral‐at‐cage molecules. An unprecedented organocatalytic asymmetric entry to a range of inherently chiral prism‐like cages via phosphonium‐containing foldamer catalysis was developed. The utilization of this protocol enables the remote desymmetric functionalization of prochiral cages with high levels of enantioselectivities. Notably, diverse late‐stage molecular editing of chiral prism‐like cages was primed for an array of high‐value chiral compounds.