Metal-free arylation of ethyl acetoacetate with hypervalent diaryliodonium salts: an immediate access to diverse 3-aryl-4(1H)-quinolones

J Org Chem. 2015 Mar 6;80(5):2513-2520. doi: 10.1021/jo5023958. Epub 2015 Feb 24.

Abstract

A clean arylation protocol of ethyl acetoacetate was developed using hypervalent diaryliodonium salts under mild and metal-free conditions. The scope of the reaction, using symmetric and unsymmetric iodonium salts with varying sterics and electronics, was examined. Further, this method has been applied for the synthesis of antimalarial compound ELQ-300, which is currently in preclinical development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetoacetates / chemistry*
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Iodine / chemistry*
  • Metals / chemistry*
  • Molecular Structure
  • Onium Compounds / chemistry*
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology*

Substances

  • 6-Chloro-7-methoxy-2-methyl-3-(4-(4-(trifluoromethoxy)phenoxy)phenyl)quinolin-4(1H)-one
  • Acetoacetates
  • Antimalarials
  • Metals
  • Onium Compounds
  • Quinolines
  • Quinolones
  • Iodine
  • ethyl acetoacetate