One-Pot Sequential [3 + 3] Dipolar Cycloaddition of Aldehyde or Ketone and Hydroxylamine with Spirocyclopropyl Oxindole

A Sc­(OTf)3-catalyzed highly diastereoselective one-pot sequential [3 + 3] dipolar cycloaddition reaction of aldehyde or ketone, N-alkyl hydroxylamine, and spirocyclopropyl oxindole is developed, allowing facile construction of spirocyclic oxindole-tetrahydro-1,2-oxazines with sufficient structural...

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Bibliographic Details
Published in:Journal of organic chemistry 2018-10, Vol.83 (20), p.12763-12774
Main Authors: Xu, Peng-Wei, Chen, Chen, Liu, Jia-Kuan, Song, Yu-Ting, Zhou, Feng, Yan, Jun, Zhou, Jian
Format: Article
Language:English
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Summary:A Sc­(OTf)3-catalyzed highly diastereoselective one-pot sequential [3 + 3] dipolar cycloaddition reaction of aldehyde or ketone, N-alkyl hydroxylamine, and spirocyclopropyl oxindole is developed, allowing facile construction of spirocyclic oxindole-tetrahydro-1,2-oxazines with sufficient structural diversity. The corresponding catalytic enantioselective one-pot protocol of aldehydes is also reported, affording the desired adducts in up to 97% ee. The biological evaluation of selected oxindole-based spirocyclic tetrahydro-1,2-oxazines revealed that they exerted cytotoxic effects on human prostate cancer cells with the capacity to inhibit NFκB signaling in prostate cancer cells.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.8b02208