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

Peng-Wei Xu; Chen Chen; Jia-Kuan Liu; Yu-Ting Song; Feng Zhou; Jun Yan; Jian Zhou

doi:10.1021/acs.joc.8b02208

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

J Org Chem. 2018 Oct 19;83(20):12763-12774. doi: 10.1021/acs.joc.8b02208. Epub 2018 Oct 3.

Authors

Peng-Wei Xu, Chen Chen, Jia-Kuan Liu¹, Yu-Ting Song¹, Feng Zhou, Jun Yan^{1

2}, Jian Zhou³

Affiliations

¹ MOE Key Laboratory of Model Animals for Disease Study , Model Animal Research Center of Nanjing University , Nanjiang 210093 , China.
² State Key Laboratory of Pharmaceutical Biotechnology , Nanjing University , Nanjing 210093 , P. R. China.
³ State Key Laboratory of Organometallic Chemistry , Shanghai Institute of Organic Chemistry , Shanghai 200032 , P. R. China.

PMID: 30240218
DOI: 10.1021/acs.joc.8b02208

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't