Suzuki−Miyaura Cross-Coupling Reactions Mediated by Palladium/Imidazolium Salt Systems

Abstract

Nucleophilic N-heterocyclic carbenes (NHC) have been used as ancillary ligands in palladium-mediated Suzuki−Miyaura cross-coupling reactions involving aryl chlorides or aryl triflates with arylboronic acids. The scope of the coupling process using Pd(0) or Pd(II) sources and an imidazolium salt in the presence of a base, Cs2CO3, was tested using various substrates. The Pd(OAc)2 or Pd2(dba)3/IMes·HCl (2, IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) system presents very high activity with respect to electron-neutral and electron-rich aryl chlorides. The ligand IPr·HCl (3, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) is also effective for the Suzuki−Miyaura cross-coupling involving a wide spectrum of aryl chlorides and aryl triflates. The general protocol developed has been applied successfully to the synthesis of an antiinflammatory drug (Fenbufen) and to a key intermediate in the synthesis of sartans. Mechanistically, palladium-to-ligand ratio studies support an active palladium species bearing one nucleophilic carbene ligand.