Insights into Sonogashira cross-coupling by high-throughput kinetics and descriptor modeling.
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.
an der Heiden
Markus R
MR
Inorganic Chemistry, Zintl-Institute, Darmstadt University of Technology, Petersenstrasse 18, 64287 Darmstadt, Germany.
Plenio
Herbert
H
Immel
Stefan
S
Burello
Enrico
E
Rothenberg
Gadi
G
Hoefsloot
Huub C J
HC
D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry*; D006842:Hydrocarbons, Brominated / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D015394:Molecular Structure; D010720:Phosphines / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
D000480:Alkynes; D003432:Cross-Linking Reagents; D006842:Hydrocarbons, Brominated; D008024:Ligands; D010720:Phosphines; D003300:Copper; C044646:phosphine