Asymmetric Synthesis of Chiral Calix[4]arenes with Both Inherent and Axial Chirality via Cobalt‐Catalyzed Enantioselective Intermolecular C−H Annulation

• Published in: Angewandte Chemie International Edition 2024-12, Vol.63 (52), p.e202412459-n/a
• Main Authors: Qian, Pu‐Fan, Zhou, Gang, Hu, Jia‐Heng, Wang, Bing‐Jie, Jiang, Ao‐Lian, Zhou, Tao, Yuan, Wen‐Kui, Yao, Qi‐Jun, Chen, Jia‐Hao, Kong, Ke‐Xin, Shi, Bing‐Feng
• Format: Article
• Language: English
• Subjects: calixarene; enantioselective C−H activation; inherent chirality; octahedral cobalt catalysis; salicyloxazoline
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202412459

Inherently chiral calixarenes have garnered significant attention due to their distinctive properties, yet the development of efficient catalytic asymmetric synthesis methods remains a critical challenge. Herein, we report the asymmetric synthesis of calix[4]arenes featuring inherent or both inherent and axial chirality via a cobalt‐catalyzed C−H activation/annulation strategy in high yield with excellent enantio‐ and diastereoselectivity (up to >99 % ee and >20 : 1 dr). Electrooxidation was also suitable for this transformation to obviate the sacrificial metal oxidants, underscoring the environmentally friendly potential of this approach. A key octahedral cobaltacycle intermediate was synthesized and characterized, providing valuable insights into the mode of enantio‐ and diastereocontrol of this protocol. Noteworthy photoluminescence quantum yields of up to 0.94 were measured, underscoring the potential of these compounds in the domain of organic fluorescent materials. An unprecedented protocol for the asymmetric synthesis of calix[4]arenes through enantioselective cobalt‐catalyzed C−H annulation is reported. A broad range of inherently chiral calix[4]arenes with noteworthy optical properties (ΦF up to 0.94) have been constructed in good yields with excellent enantioselectivities (72 examples, up to 99 % yield and up to >99 % ee).