Sequential coupling/desilylation-coupling/cyclization in a single pot under Pd/C-Cu catalysis: synthesis of 2-(hetero)aryl indoles

Org Biomol Chem. 2011 May 21;9(10):3808-16. doi: 10.1039/c0ob01161d. Epub 2011 Mar 29.

Abstract

A new one-pot synthesis of 2-(hetero)aryl indoles via sequential C-C coupling followed by C-Si bond cleavage and a subsequent tandem C-C/C-N bond forming reaction is described. A variety of functionalized indole derivatives were prepared by conducting this four step reaction under Pd/C-Cu catalysis. The methodology involved coupling of (trimethylsilyl)acetylene with iodoarenes in the presence of 10% Pd/C-CuI-PPh(3) and triethylamine in MeOH, followed by treating the reaction mixture with K(2)CO(3) in aqueous MeOH, and finally coupling with o-iodoanilides. The single crystal X-ray data of a synthesized indole derivative is presented. Application of the methodology, in vitro pharmacological properties of the synthesized compound, along with a docking study is described.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon / chemistry*
  • Catalysis
  • Copper / chemistry*
  • Cyclization
  • Enzyme Activation / drug effects
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Models, Molecular
  • Molecular Conformation
  • Palladium / chemistry*
  • Silicon / chemistry*
  • Sirtuin 1 / metabolism

Substances

  • Indoles
  • Palladium
  • Carbon
  • Copper
  • SIRT1 protein, human
  • Sirtuin 1
  • Silicon