Modulating reactivity and diverting selectivity in palladium-catalyzed heteroaromatic direct arylation through the use of a chloride activating/blocking group

J Org Chem. 2010 Feb 19;75(4):1047-60. doi: 10.1021/jo902515z.

Abstract

Through the introduction of an aryl chloride substituent, the selectivity of palladium-catalyzed direct arylation may be diverted to provide alternative regioisomeric products in high yields. In cases where low reactivity is typically observed, the presence of the carbon-chlorine bond can serve to enhance reactivity and provide superior outcomes. From a strategic perspective, the C-Cl bond is easily introduced and can be employed in a variety of subsequent transformations to provide a wealth of highly functionalized heterocycles with minimal substrate preactivation. The impact of the C-Cl functional group on direct arylation reactivity has also been evaluated mechanistically, and the observed reactivity profiles correlate very well with that predicted by a concerted metalation-deprotonation pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Chlorides / chemistry*
  • Cross-Linking Reagents / chemistry*
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Palladium / chemistry*
  • Stereoisomerism

Substances

  • Chlorides
  • Cross-Linking Reagents
  • Heterocyclic Compounds
  • Palladium