Aryne [3 + 2] cycloaddition with N-sulfonylpyridinium imides and in situ generated N-sulfonylisoquinolinium imides: a potential route to pyrido[1,2-b]indazoles and indazolo[3,2-a]isoquinolines

Org Biomol Chem. 2012 Mar 7;10(9):1922-30. doi: 10.1039/c2ob06611d. Epub 2012 Jan 25.

Abstract

The aryne [3 + 2] cycloaddition process with pyridinium imides breaks the aromaticity of the pyridine ring. By equipping the imide nitrogen with a sulfonyl group, the intermediate readily eliminates a sulfinate anion to restore the aromaticity, leading to the formation of pyrido[1,2-b]indazoles. The scope and limitation of this reaction are discussed. As an extension of this chemistry, N-tosylisoquinolinium imides, generated in situ from N'-(2-alkynylbenzylidene)-tosylhydrazides via an AgOTf-catalyzed 6-endo-dig electrophilic cyclization, readily undergo aryne [3 + 2] cycloaddition to afford indazolo[3,2-a]-isoquinolines in the same pot, offering a highly efficient route to these potential anticancer agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclization
  • Imides / chemistry*
  • Indazoles / chemistry*
  • Isoquinolines / chemistry*
  • Molecular Structure
  • Nitrogen / chemistry
  • Phenazopyridine / chemistry*
  • Sulfur Compounds / chemistry*

Substances

  • Imides
  • Indazoles
  • Isoquinolines
  • Sulfur Compounds
  • Phenazopyridine
  • Nitrogen