Chu Anqi, Zhu Boyan, Zhang Xiaoyong, Zhu Hanwen, Zhang Jingying, Liu Xihong
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
Institute of Systems and Physical Biology, Shenzhen Bay Laboratory, Shenzhen 518107, China.
Sci Adv. 2024 Nov 22;10(47):eadr1628. doi: 10.1126/sciadv.adr1628.
Despite the considerable potential applications for helically chiral molecules across various sectors, their catalytic asymmetric synthesis remains nascent and has seen very limited advancement compared to that of central and axial chiral compounds, primarily owing to the scarcity of available starting materials and the immense challenges associated with achieving stereochemical control. Herein, we report an innovative approach to the facile synthesis and catalytic kinetic resolution of uniquely structured and stereochemically complex helical polycyclic phenols by using a steric hindrance-regulated enantioselective dearomative amination reaction. The distinguished aspects of this method include the exceptional stability of the dearomatized products and impressive versatility of the recovered substrates in the construction of enantioenriched helical frameworks. This work showcases that the strategic incorporation of appropriate steric groups near the reaction site of an electron-rich aromatic compound can indeed enable an interrupted Friedel-Crafts reaction, thus opening an alternate avenue for the study of dearomatization in nonfunctionalized arenes.
尽管螺旋手性分子在各个领域具有相当大的潜在应用，但与中心手性和轴手性化合物相比，它们的催化不对称合成仍处于起步阶段，进展非常有限，主要原因是可用起始原料稀缺以及实现立体化学控制面临巨大挑战。在此，我们报告了一种创新方法，通过空间位阻调节的对映选择性去芳构化胺化反应，轻松合成并催化动力学拆分结构独特且立体化学复杂的螺旋多环酚。该方法的显著特点包括去芳构化产物的卓越稳定性以及回收底物在构建对映体富集螺旋骨架方面令人印象深刻的多功能性。这项工作表明，在富电子芳香化合物的反应位点附近战略性地引入适当的空间基团确实能够实现中断的傅克反应，从而为研究未官能化芳烃中的去芳构化开辟了一条替代途径。
