TMEDA-assisted effective direct ortho arylation of electron-deficient N-heteroarenes with aromatic Grignard reagents

J Org Chem. 2013 Apr 5;78(7):3243-9. doi: 10.1021/jo400152f. Epub 2013 Mar 19.

Abstract

In the addition of TMEDA in toluene, aryl Grignards could effectively and site-specifically ortho-arylate electron-deficient heteroarenes under mild conditions. This endeavor successfully changed the old low-yielding reaction, aryl Grignard addition to N-heteroarenes, into an efficient procedure for heterobiaryls. The combination of the inexpensive aryl Grignards, TMEDA, the cost-free air, no use of any transition-metal catalyst, the mild reaction conditions, and the high-yielding gram-scale results enables this new procedure to be cost-effective and potentially utilizable in industry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electrons
  • Ethylenediamines / chemistry*
  • Heterocyclic Compounds / chemistry*
  • Molecular Structure
  • Organometallic Compounds / chemistry*
  • Pyridines / chemistry*
  • Quinolines / chemistry*
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / chemistry
  • Toluene / chemistry

Substances

  • Ethylenediamines
  • Heterocyclic Compounds
  • Organometallic Compounds
  • Pyridines
  • Quinolines
  • Quinoxalines
  • N,N,N',N'-tetramethylethylenediamine
  • Toluene