Regioselective synthesis of 1,4-disubstituted imidazoles

Org Biomol Chem. 2012 Feb 7;10(5):1079-87. doi: 10.1039/c1ob06690k. Epub 2011 Dec 15.

Abstract

A short and efficient synthesis of 1,4-disubstituted imidazoles has been developed which provides the desired products with complete regioselectivity. This protocol allows preparation of compounds which are challenging to prepare by current literature methods in a regioselective fashion, a sterically and electronically diverse range of N-substituents being accessible. The sequence involves an unusual double aminomethylenation of a glycine derivative, to yield a 2-azabuta-1,3-diene, onto which addition of an amine nucleophile results in a transamination/cyclization to prepare the substituted imidazole. The cyclization event is surprisingly insensitive to steric and electronic variations on the amine component, enabling a diverse range of imidazoles to be prepared.

MeSH terms

  • Chemistry Techniques, Synthetic
  • Cyclization
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry*
  • Stereoisomerism

Substances

  • Imidazoles