Regioselectivity of Larock heteroannulation: a contribution from electronic properties of diarylacetylenes

J Org Chem. 2013 Dec 20;78(24):12703-9. doi: 10.1021/jo402304s. Epub 2013 Dec 5.

Abstract

A series of 2,3-diarylindoles were synthesized from 2-iodoaniline and unsymmetrical diarylacetylenes using the Larock heteroannulation. Diarylacetylenes bearing electron-withdrawing substituents lead to 2,3-diarylindoles with substituted phenyl moieties at the 2-position as major products, while those with electron-donating groups preferably yield indole products with substituted phenyl moieties at the 3-position. The regioisomeric product ratios exhibit a clear correlation with Hammett σ(p) values. DFT calculations reveal the origin of this effect, displaying smaller activation energy barriers for those pathways leading to the major regioisomer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Aniline Compounds / chemistry
  • Electrons
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Models, Molecular
  • Molecular Structure
  • Quantum Theory
  • Stereoisomerism

Substances

  • 2-iodobenzenamine
  • Alkynes
  • Aniline Compounds
  • Indoles