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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Synthesis of CF3-Containing Bispirocyclic 2-Pyrrolidinones through Cycloaddition and Oxidative Dearomatization from
Shan Chen1, Yong-Le Chen1, Yan Li1
1Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, University Engineering Research Center for Chemistry of Characteristic Medicinal Resources (Guangxi), School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin541004, China.
Abstract:
Herein, a variety of trifluoromethyl-containing bispirocyclic 2-pyrrolidinones were prepared in good yields with high diastereoselectivity through a cinchonidine-catalyzed (4 + 3) cycloaddition and oxidative dearomatization strategy from N-trifluoromethyl aryl nitrones and 1-alkynyl-2-naphthols under mild reaction conditions. Mechanistic studies revealed that PhI(OAc)2 played important roles in the formation of CF3-containing bispirocyclic 2-pyrrolidinones in the oxidation and dearomatization steps. The present method features high regioselectivity and diastereoselectivity, three rings and three carbon stereocenters formation, and novel bispirocyclic 2-pyrrolidinone scaffolds.
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