Imine Ligand-Promoted And Ligand-free Palladium-Catalyzed Suzuki Reactions

The palladium-catalyzed Suzuki reaction of aryl halides with aryl boronic acids is one of the most important carbon-carbon bond formation reactions and has become an indispensable tool in modern organic synthesis for the preparation of biaryl compounds. The Suzuki reaction has been broadly applied to the synthesis of natural products, pharmaceuticals, as well as the advanced functional materials due to its high efficiency and wide applicability to substrates.Generally, the Suzuki reaction is a ligand-promoted reaction. The electric-rich, steric phosphine ligands, N-Heterocyclic Carbene ligands (NHC) and palladacycles are commonly used in the Suzuki reaction. In recent years, bidentate ligands arouse widespread interest because of the hemilability and have been applied to a variety of palladium-catalyzed transformations. To obtain high catalytic activity, 2, 6-diisopropyl aniline was used to synthesize efficient ligand for the Suzuki reaction due to its large steric hinderance. Currently, green chemistry has become a research hot-point. The use of water as solvent or cosolvent instead of traditional organic solvents is the important and efficient strategy in green chemistry. Moreover, the development of "ligand-free" catalytic systems has become one of the most challenging fields in synthetic organic chemistry, because they are simple and cheap, more importantly, the "ligand-free" catalytic system makes it possible to carry out the Suzuki reaction under an aerobic atmosphere and/or in an aqueous media. However, there is still no systematic research about the influence of reaction atmosphere on the Suzuki reaction in aqueous media under ligand-free conditions. In this paper, we discussed the Suzuki reaction on the following three catalytic systems.1. Based on the steric hinderance of 2, 6-diisopropyl aniline and the hemilability of the bidentate ligand, we synthesized an air-stable iminophosphine ligandâ… , and obtained its crystal structure for the first time. The catalytic system could activate aryl chlorides, and the reaction between 2-chloronitrobenzene and phenyl boronic acid was completed quantitatively in 10 h with 1 mol % Pd₂(dba)₃.2. On the basis of hemilability of the bidentate ligand and the concept of green chemistry, we designed and synthesized a new type of air-stable water-soluble iminc ligandâ…¡and obtained its crystal structure. The system showed high catalytic activity towards aryl bromides at room temperature. Using 1 mol % PdCl₂, the reaction of 4-bromoanisole and 4-tolyl boronic acid could be completed in 5 min with a high turnover frenquency (TOF) up to 1200 h^-1.3. An efficient protocol of PdCl₂-H₂O/EtOH system has been developed for the Suzuki reaction of deactivated aryl bromides or heteroaryl bromides with aryl boronic acids, respectively. The phenomenon of oxygen-promotion was observed. To the best of our knowledge, this is the first report of oxygen-promoted palladium-catalyzed ligand-free Suzuki reaction in aqueous media. In the case of the coupling of 4-bromoanisole with phenyl boronic acid, the highest TOF was reached up to 1500 h^-1. The Suzuki reaction between 2-bromopyridine and 4-tolyl boronic acid was completed quantitatively in 10 min.