Enantioselective Synthesis of Spirocyclopentane Oxindoles Bearing Five Consecutive Stereocenters through Secondary Amine‐Catalyzed [3+2] Cycloaddition

• Published in: European journal of organic chemistry Vol. 2022; no. 20
• Main Authors: Zhou, Jing‐Wei, Chen, Ben‐Hong, Zhang, Feng‐Hua, Xue, Jing, He, Xiang‐Hong, Peng, Cheng, Huang, Wei, Zhao, Qian
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 25.05.2022; Wiley Subscription Services, Inc
• Subjects: Aldehydes; Asymmetric synthesis; Cascade chemical reactions; Chemistry; Chemistry, Organic; Cycloaddition; Diketones; Enantiomers; Five consecutive stereocenters; Michael/Michael cascade reaction; Physical Sciences; Science & Technology; Secondary amine-catalyzed; Spirocyclopentane oxindoles; REVISION; Michael cascade reaction; Spirocyclopentane oxindoles; ASYMMETRIC-SYNTHESIS; Five consecutive stereocenters; STEREOCHEMISTRY; CASCADE; DISCOVERY; SPIROOXINDOLES; Asymmetric synthesis; Michael; CONSTRUCTION; SCAFFOLDS; DERIVATIVES; Secondary amine-catalyzed
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202200489

This work delineates a Michael‐initiated ring‐closing [3+2] cycloaddition of newly designed 3‐(1‐benzyl‐2‐oxoindolin‐3‐yl)pentane‐2,4‐diones with α,β‐unsaturated aldehydes. During the chiral secondary amine‐catalyzed cascade reaction, highly functionalized spirocyclopentane oxindole derivatives containing five consecutive stereogenic centers were formed, two of which were tetrasubstituted carbon. All the desired products are smoothly obtained in good yields (up to 90 %) with excellent enantioselectivities (up to >99 : 1 er) and diastereoselectivities (up to >95 : 5 dr). Meanwhile, the practicality of this strategy was highlighted by the further gram‐scale experiment and a set of synthetic transformations. Multi‐functionalized spirocyclopentane oxindoles represent the characteristic structural core in ubiquitous bioactive compounds. However, the enantioselective synthesis of spirooxindole‐fused cyclopentanes containing five adjacent stereocenters is rare in the literature. Here, a secondary amine‐catalyzed [3+2] cycloaddition between C3‐substituted oxindoles and α,β‐unsaturated aldehydes to afford highly functionalized spirocyclopentaneoxindole derivatives bearing five consecutive stereocenters is reported.