Cu(II)-catalyzed direct and site-selective arylation of indoles under mild conditions

J Am Chem Soc. 2008 Jul 2;130(26):8172-4. doi: 10.1021/ja801767s. Epub 2008 Jun 11.

Abstract

We have developed a new site-selective Cu(II)-catalyzed C-H bond functionalization process that can selectively arylate indoles at either the C3 or C2 position under mild conditions. The scope of the arylation process is broad and tolerates broad functionality on both the indole and aryl unit, which makes it amenable to further elaboration. The mechanism of the arylation reaction is proposed to proceed via a Cu(III)-aryl species that undergoes initial electrophilic addition at the C3 position of the indole motif. We speculate that site of indole arylation arises through a migration of the Cu(III)-aryl group from C3 to C2, and this can be controlled by the nature of the group on the nitrogen atom; free (NH)- and N-alkylindoles deliver the C3-arylated product, whereas N-acetylindoles afford the C2 isomer, both with excellent yield and selectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Copper*
  • Hydrocarbons, Aromatic / chemistry*
  • Indoles / chemistry*

Substances

  • Hydrocarbons, Aromatic
  • Indoles
  • Copper