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

Peng-Wei XuChen ChenJia-Kuan LiuYu-Ting SongFeng ZhouJun YanJian Zhou
Published in: The Journal of organic chemistry (2018)
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.
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