Organocatalytic Synthesis of Methylene-Bridged N-Heterobiaryls

Org Lett. 2016 Nov 18;18(22):5808-5811. doi: 10.1021/acs.orglett.6b02719. Epub 2016 Nov 3.

Abstract

A one-step synthesis of 1,1'- and 2,2'-methylene-bridged N-heterobiaryls directly from the corresponding N-heterocycles in a reaction with methylmagnesium chloride in the presence of catalytic amounts of N,N,N',N'-tetramethylethylenediamine under thermal and microwave conditions is reported. The split-and-merge methylenation of 2,2'-N-heterobiaryls and the direct ortho-alkylation of quinoline and isoquinoline with Grignard reagents have also been developed. Mechanistic studies identified several intermediates and provided insight into the formation and roles of magnesium hydride species in the process.

Publication types

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

MeSH terms

  • Catalysis
  • Chemistry Techniques, Synthetic / methods*
  • Ethylenediamines / chemistry*
  • Heterocyclic Compounds, Bridged-Ring / chemical synthesis*
  • Heterocyclic Compounds, Bridged-Ring / chemistry
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Molecular Structure

Substances

  • Ethylenediamines
  • Heterocyclic Compounds, Bridged-Ring
  • Isoquinolines
  • N,N,N',N'-tetramethylethylenediamine