Insights into Sonogashira cross-coupling by high-throughput kinetics and descriptor modeling

Chemistry. 2008;14(9):2857-66. doi: 10.1002/chem.200701418.

Abstract

A method is presented for the high-throughput monitoring of reaction kinetics in homogeneous catalysis, running up to 25 coupling reactions in a single reaction vessel. This method is demonstrated and validated on the Sonogashira reaction, analyzing the kinetics for almost 500 coupling reactions. First, one-pot reactions of phenylacetylene with a set of 20 different meta- and para-substituted aryl bromides were analyzed in the presence of 17 different Pd-phosphine complexes. In addition, the temperature-dependent Sonogashira reactions were examined for 21 different ArX (X=Cl, Br, I) substrates, and the corresponding activation enthalpies and entropies were determined by means of Eyring plots: ArI (DeltaH(not equal)=48-62 kJ mol(-1); DeltaS(not equal)=-71--39 J mol(-1) K; NO(2)-->OMe), ArBr (DeltaH(not equal)=54-82 kJ mol(-1), DeltaS(not equal)=-55-11 J mol(-1) K), and ArCl (DeltaH(not equal)=95-144 kJ mol(-1), DeltaS(not equal)=-6-100 J mol(-1) K). DFT calculations established a linear correlation of DeltaH( not equal) and the Kohn-Sham HOMO energies of ArX (X=Cl, Br, I) and confirmed their involvement in the rate-limiting step. However, despite different C--X bond energies, aryl iodides and electron-deficient aryl bromides showed similar activation parameters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemical synthesis*
  • Alkynes / chemistry*
  • Catalysis
  • Copper / chemistry
  • Cross-Linking Reagents / chemical synthesis*
  • Cross-Linking Reagents / chemistry*
  • Hydrocarbons, Brominated / chemistry*
  • Kinetics
  • Ligands
  • Models, Chemical*
  • Molecular Structure
  • Phosphines / chemistry
  • Temperature
  • Time Factors

Substances

  • Alkynes
  • Cross-Linking Reagents
  • Hydrocarbons, Brominated
  • Ligands
  • Phosphines
  • Copper
  • phosphine