Yuan Mengyao, Xie Wansen, Yu Shaoze, Liu Tong, Yang Xiaoyu
School of Physical Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
Lingang Laboratory, Shanghai, 200031, China.
Nat Commun. 2025 Apr 26;16(1):3943. doi: 10.1038/s41467-025-59221-3.
Inherently chiral calix[4]arenes represent a distinct class of chiral frameworks whose chirality arises from the dissymmetry of the entire molecule. Although these chiral scaffolds have been widely applied in various research fields, their catalytic enantioselective synthesis remains largely underexplored. Herein, we report the enantioselective synthesis of inherently chiral calix[4]arenes using an organocatalyzed desymmetrization method. By using chiral phosphoric acid catalysis, the asymmetric electrophilic amination reactions of the phenol-containing prochiral calix[4]arenes led to a range of inherently chiral calix[4]arenes with high yields and enantioselectivities. Significantly, the practicability of this method is underscored by its successful implementation using as little as 0.05 mol% of chiral catalyst, without compromising reaction efficiency and enantioselectivity. Moreover, the aminophenol moiety in the products could be easily modified to produce unique calix[4]arenes with diverse N,O-heterocycles, as well as the simple meta-amino-substituted chiral calix[4]arene, which have shown promising potential in the development of new chiral catalysts.
固有手性杯[4]芳烃代表了一类独特的手性骨架，其手性源于整个分子的不对称性。尽管这些手性支架已广泛应用于各个研究领域，但其催化对映选择性合成在很大程度上仍未得到充分探索。在此，我们报道了使用有机催化去对称化方法对固有手性杯[4]芳烃进行对映选择性合成。通过手性磷酸催化，含酚前手性杯[4]芳烃的不对称亲电胺化反应产生了一系列高产率和对映选择性的固有手性杯[4]芳烃。值得注意的是，该方法的实用性体现在仅使用低至0.05 mol%的手性催化剂就能成功实现，且不影响反应效率和对映选择性。此外，产物中的氨基酚部分可以很容易地进行修饰，以制备具有各种N，O - 杂环的独特杯[4]芳烃，以及简单的间氨基取代手性杯[4]芳烃，它们在新型手性催化剂的开发中显示出了广阔的前景。
