Highly convenient amine-free sonogashira coupling in air in a polar mixed aqueous medium by trans- and cis-[(NHC)2PdX2] (X = Cl, Br) complexes of N/O-functionalized N-heterocyclic carbenes

Article abstract of DOI:10.1002/chem.200800301

Two new trans- and cis[(NHC)₂PdX₂] (X = Cl, Br) complexes of MO-functionalized N-heterocyclic carbenes employed in a highly convenient amine-free Sonogashira cross-coupling reaction in air in a polar mixed aqueous medium are reported. Specifically, the trans-[{1-benzyl-3-(3,3- dimethyl-2-oxobutyl)imidazol-2-ylidene}₂PdBr₂] (3) and cw-[{l-benzyl-3-(N-ferf-butylacetamido)imidazol-2-ylid-ene}₂PdCl ₂] (4) complexes effectively catalyzed the Sonogashira cross-coupling reaction of aryl iodides with substituted acetylenes in air in a mixed solvent (DMF/H₂O, 3:1 v/v) under amine-free conditions. Interestingly, these trans- and c/s-[(NHC)₂PdX₂] (X = Cl, Br) complexes, with two N-heterocyclic carbene ligands, exhibited superior activity compared with the now popular PEPPSI (pyridine enhanced precatalyst preparation, stabilization and initiation)-themed analogues, trans-[(NHC)Pd(pyridine)X₂] (X = Cl, Br), 3a and 4a, with one N-heterocyclic carbene ligand and a "throw away" pyridine ligand in a trans disposition to each other. The higher activities of 3 and 4 compared with PEPPSI analogues 3a and 4a are attributed to more-electron-rich metal centers, as revealed by DFT studies, in the former complexes and is in concurrence with a more electron-rich metal center being effective in facilitating the oxidative addition of aryl halide, often a rate-determining step in palladium-mediated cross-coupling reactions. Complexes 3 and 4 were prepared from the corresponding silver analogues by transmetalation with [(COd)PdCl₂], whereas the corresponding PEPPSI analogues 3a and 4a were obtained directly from the imidazolium halide salts by reaction with PdCl₂ in pyridine in the presence of K₂CO₃ as base.