Citation: Mengyao Yuan, Wansen Xie, Xiaoyu Yang. Enantioselective synthesis of inherently chiral calix[4]arenes via asymmetric C-H bromination of phenols[J]. Chinese Chemical Letters, ;2026, 37(9): 112157. doi: 10.1016/j.cclet.2025.112157 shu

Enantioselective synthesis of inherently chiral calix[4]arenes via asymmetric C-H bromination of phenols

Mengyao Yuan ^{a, b} ,
Wansen Xie ^a ,
Xiaoyu Yang ^{a, c, *,}

a.
School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China
b.
Lingang Laboratory, Shanghai 200031, China
c.
State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China

yangxy1@shanghaitech.edu.cn

Received Date: 19 July 2025
Revised Date: 12 November 2025
Accepted Date: 21 November 2025
Available Online: 22 November 2025

Figures(6)

Inherently chiral calix[4]arenes (ICCs) represent a unique class of chiral macrocyclic arenes, which hold significant potentials in chiral recognition, sensing, and asymmetric catalysis. However, accessing these distinct chiral molecules poses notable challenges, with their catalytic enantioselective synthesis being largely underdeveloped. Herein, we report an efficient enantioselective synthesis of ICCs using an asymmetric C-H brominative desymmetrization strategy. Utilizing the chiral phosphoric acid-catalyzed asymmetric electrophilic aromatic ortho-bromination reaction of phenol, we successfully broke the symmetry of prochiral calix[4]arenes, which resulted in the formation of various 1,3-bis-phenyl rings-substituted ICCs with good yields and high enantioselectivities. Moreover, the asymmetric di-bromination of bis-phenol-containing prochiral calix[4]arenes was demonstrated, yielding ICCs featuring three or even four rings displaying various modifications with high enantioselectivity. Leveraging the versatility of the introduced bromide handle and the phenolic hydroxyl group in the ICC products, a range of derivatizations were performed to produce diverse ICC derivatives, one of which exhibited notable chiroptical properties, highlighting the significance of this method.
- Inherently chiral calix[4]arenes,
- Enantioselective desymmetrization,
- Asymmetric organocatalysis,
- Electrophilic bromination,
- Chiral phosphoric acid
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