Wang Bai-Lin, Yu Jie-Qiang, Zhang Qian, Wang Xing-Wang
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. China.
College of Materials, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 310036, P. R. China.
JACS Au. 2025 Apr 30;5(5):2159-2171. doi: 10.1021/jacsau.5c00069. eCollection 2025 May 26.
A Cu-(II)-catalyzed asymmetric cascade process was successfully developed by the dimerization of β,γ-unsaturated α-keto tryptophol esters or β,γ-unsaturated α-keto tryptamino amides under mild reaction conditions, furnishing the corresponding macrocyclic dilactones and dilactams in good yields with excellent regio-, diastereo-, and enantioselectivities. The transformation involved a four-step cascade of double Friedel-Crafts alkylation and double -hemiketalization, providing efficient access to a variety of macrocyclic dilactone and dilactam scaffolds bearing four new stereocenters in a one-pot and highly atom-economic fashion. The resultant chiral macrocyclic compounds were further applied as ligands in the copper-catalyzed asymmetric Friedel-Crafts alkylation reactions and also tested as multifunctional chiral host molecules in binding with quinine and quinidine.
通过β，γ-不饱和α-酮色醇酯或β，γ-不饱和α-酮色氨酰胺在温和反应条件下的二聚反应，成功开发了一种铜（II）催化的不对称串联反应，以良好的收率、出色的区域选择性、非对映选择性和对映选择性得到相应的大环双内酯和双内酰胺。该转化过程涉及双傅克烷基化和双半缩酮化的四步串联反应，以一锅法和高原子经济性的方式提供了有效合成多种带有四个新立体中心的大环双内酯和双内酰胺骨架的方法。所得手性大环化合物进一步用作铜催化不对称傅克烷基化反应的配体，并作为多功能手性主体分子用于与奎宁和奎尼丁的结合测试。
