Enantioselective [4 + 1] Annulation Reactions of α-Substituted Ammonium Ylides To Construct Spirocyclic Oxindoles

J Am Chem Soc. 2015 Jul 29;137(29):9390-9. doi: 10.1021/jacs.5b04792. Epub 2015 Jul 16.

Abstract

Ammonium ylides have a long history in organic synthesis, but their application in asymmetric catalysis is still underdeveloped in regard to both substrate scope and reaction pathways compared with phosphorus and sulfur ylides. Here a previously unreported asymmetric [4 + 1] annulation reaction of 3-bromooxindoles and electron-deficient 1-azadienes has been developed through ammonium ylide catalysis of a newly designed 2'-methyl α-isocupreine (α-MeIC), efficiently delivering spirocyclic oxindole compounds incorporating a dihydropyrrole motif in excellent enantioselectivity (up to 99% ee). To the best of our knowledge, this work represents the first example of asymmetric catalysis of ammonium ylides bearing α-substitutions, and the catalytic [4 + 1] annulation pathway of ammonium ylides is also unprecedented. Moreover, (1)H NMR, mass spectroscopy, and computational calculation studies were conducted, and the catalytic cycle and a tentative explanation of the enantioselective mechanism have been successfully elucidated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonium Compounds / chemistry*
  • Catalysis
  • Indoles / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Oxindoles
  • Stereoisomerism

Substances

  • Ammonium Compounds
  • Indoles
  • Oxindoles
  • 2-oxindole