Enantioselective Construction of Spiro[2 H ‐pyran‐3,4′‐indoline] by a Systematic Michael/Reduction/Cyclization Sequence Triggered by the Asymmetric Conjugate Addition of Ketones to Isatylidenemalononitriles

作者：Hua Zhao, Yu‐Bao Lan, Zhaomin Liu, Yong Wang, Xing‐Wang Wang, Jing‐Chao Tao · 发表于：European Journal of Organic Chemistry · 年份：2012 · DOI：10.1002/ejoc.201101810 · 被引用次数：43 · 研究领域：Asymmetric Synthesis and Catalysis、Chemical synthesis and alkaloids、Synthetic Organic Chemistry Methods

Abstract Heterocyclic spirooxindoles that bear a multisubstitutedheterocyclic motif and quaternary stereocenter at the 3‐position are prevalent in a large number of spirooxindole alkaloids, which are pharmaceutically relevant compounds with remarkable biological activities. In this paper, we report an efficient method for the construction of enantiomerically enriched spiro[2 H ‐pyran‐3,4′‐indoline] derivatives by a systematic Michael/reduction/cyclization sequence. The initial Michael addition of isatylidenemalononitriles with ketones was catalyzed by a cinchona‐based chiral primary amine and L ‐camphorsulfonic acid and furnished multifunctional, optically active Michael adducts in high yields (81–99 %) with excellent enantioselectivities (95 to >99 % ee ). Subsequently, the Michael adducts were converted into spiro[2 H ‐pyran‐3,4′‐indoline] derivatives in 52–93 % yields with 1.5:1 to 20:1 diastereomeric ratio and 90–99 % ee by utilizing NaBH 4 as a cascade reduction/cyclization reagent.