Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Aug 24;21(9):1113.
doi: 10.3390/molecules21091113.

Efficient Synthesis of Fully Substituted Pyrrolidine-Fused 3-Spirooxindoles via 1,3-Dipolar Cycloaddition of Aziridine and 3-Ylideneoxindole

Wen Ren  1 , Qian Zhao  2 , Chuan Zheng  3 , Qiong Zhao  4 , Li Guo  5 , Wei Huang  6
Affiliations

Efficient Synthesis of Fully Substituted Pyrrolidine-Fused 3-Spirooxindoles via 1,3-Dipolar Cycloaddition of Aziridine and 3-Ylideneoxindole

Wen Ren et al. Molecules. .

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.

Keywords: 1,3-dipolar cycloaddition; aziridine; single-step reaction; spirooxindole-pyrrolidine.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of the spirooxindole-pyrrolidine framework in biologically active molecules.
Scheme 1
Scheme 1
1,3-Dipolar cycloaddition-based synthesis of spirooxindole-pyrrolidines.
Scheme 2
Scheme 2
Synthetic strategy.
Scheme 3
Scheme 3
Synthesis of pharmacologically important spiro-pyrrolidines.
Figure 2
Figure 2
X-ray structure of 3a.
See this image and copyright information in PMC

References

    1. Stevens T.S., Creighton E.M., Gordon A.B., MacNicol M. Degradation of quaternary ammonium salts Part I. J. Chem. Soc. (Resumed) 1928:3193–3197. doi: 10.1039/JR9280003193. - DOI
    1. Pellissier H. Asymmetric 1,3-dipolar cycloadditions. Tetrahedron. 2007;63:3235–3285. doi: 10.1016/j.tet.2007.01.009. - DOI
    1. Stanley L.M., Sibi M.P. Enantioselective copper-catalyzed 1,3-dipolar cycloadditions. Chem. Rev. 2008;108:2887–2902. doi: 10.1021/cr078371m. - DOI - PubMed
    1. Kissane M., Maguire A.R. Asymmetric 1,3-dipolar cycloadditions of acrylamides. Chem. Soc. Rev. 2010;39:845–883. doi: 10.1039/B909358N. - DOI - PubMed
    1. Adrio J., Carretero J.C. Recent advances in the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides. Chem. Commun. 2014;50:12434–12446. doi: 10.1039/C4CC04381B. - DOI - PubMed

MeSH terms

LinkOut - more resources