Efficient Synthesis of Fully Substituted Pyrrolidine-Fused 3-Spirooxindoles via 1,3-Dipolar Cycloaddition of
Wen Ren1, Qian Zhao2, Chuan Zheng3
1Key Laboratory of Drug Targeting and Drug Delivery Systems of Ministry of Education, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. sklb_renwen@126.com.
Abstract:
Drug-like spirocyclic scaffolds have been prepared by fusing fully functionalized pyrrolidine with oxindoles in an approach based on 1,3-dipolar cycloaddition. Reaction between aziridine and 3-ylideneoxindole generated diverse spirooxindole-pyrrolidines in good yield (up to 95%) with high diastereoselectivity (up to >20:1). The reaction also proceeded smoothly with several other synthetically useful activated trisubstituted olefins. The mild reaction conditions, short reaction times, and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting spiro-architectures.
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