One-pot synthesis of highly substituted N-fused heteroaromatic bicycles from azole aldehydes

Org Lett. 2015 Apr 17;17(8):1822-5. doi: 10.1021/ol5036936. Epub 2015 Mar 27.

Abstract

An efficient route to substituted N-fused aromatic heterocycles, including indolizines, imidazo[1,2-a]pyridines, and imidazo[1,5-a]pyridines from azole aldehydes, is reported. Wittig olefination of the aldehydes with fumaronitrile and triethylphosphine affords predominantly E-alkenes that undergo rapid cyclization upon treatment with a mild base. Substituent control of the 1-, 2-, and 3-positions of the resulting heteroaromatic bicycles is shown. Alternatively, the isolable E-alkene undergoes selective alkylation with electrophiles, followed by in situ annulation to indolizines additionally substituted at the 6-position.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Indolizines / chemical synthesis*
  • Indolizines / chemistry
  • Molecular Structure
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Stereoisomerism

Substances

  • Indolizines
  • Pyridines
  • imidazo(1,5-a)pyridine
  • imidazo(1,2-a)pyridine