Palladium Catalyzed Ligand-free Suzuki Reaction In Ethylene Glycol

The palladium catalyzed Suzuki reaction of aryl halides with arylboronic acids is one of the most powerful carbon-carbon bond forming methods. It has become an important tool for the preparation of biaryl compounds due to its high efficiency and wide applicability to substrates.Heterobiaryls are the common structural units in pharmaceuticals, natural products and advanced functional materials. Therefore, an efficient protocol for palladium catalyzed Suzuki reaction of heteroaryl halides has become one of the hotspot of research topics recently. However, N-heteroaryl halides are difficult substrates for the Suzuki reaction due to the potential coordination of the nitrogen to the active palladium species. The Suzuki reaction of this substrate usually needs steric, electric-rich organic ligands to promote. To date, the ligand-free protocol for the Suzuki reaction of N-heteroaryl halides usually encounters with either a low reactivity or a narrow scope. A highly efficient catalytic system of Pd(OAc)2/EG has been developed for the Pd(OAc)2-catalyzed ligand-free aerobic Suzuki reaction. The Suzuki reaction between 2-bromopyridine and phenylboronic acid was selected as a model reaction to optimize the reaction conditions. With the optimized conditions in hand (0.5 mol% Pd(OAc)2,2 equiv. K3PO4·7H2O, EG 4 mL,80℃, in air), a number of N-heteroaryl halides, namely,2-pyridyl bromide,3-pyridyl bromide,2-quinolyl bromide,3-quinolyl bromide, 5-pyrimidyl bromide and 2-pyrazyl chloride, were coupled with arylboronic acids efficiently to afford good to excellent yields of the corresponding products. Functional groups such as CH3, NH2, NO2, F, OCH3 and COCH3 were compatible in this catalytic system. The highest TOF value reached up to 23520 h-1 for the cross-coupling of 2-methoxyl-5-bromopyridine with phenylboronic acid in the presence of a 0.05 mol% catalyst loading in 5 min to afford 2-methoxyl-5-phenylpyridine in 98% yield. Furthermore, to explore the high efficiency of the Pd(OAc)2/EG system for the Suzuki reaction of N-heteroaryl halides, the Suzuki reaction of 2-bromopyridine with phenylboronic acid was chosen to study the effect of solvent molecular structure on the reactivity. Control experiments illustrated that using methoxyl group instead of the hydroxy group of ethylene glycol resulted in obviously decreased reactivity. It can be seen that the hydroxy groups of the solvent play an important role in the reactivity of the Suzuki reaction.4-arylsubstituted triphenylamine derivatives are important intermediates for dye-sensitized solar cells (DSSCs), organic electroluminescent diodes and fluorescent molecular probes due to the TPA structure. The catalytic system of Pd(OAc)2/EG was successfully extended for the synthesis of 4-arylsubstituted triphenylamine derivatives in air. The Suzuki reaction of N-, or S-heteroaryl halides with 4-(diphenylamino)phenylboronic acid proceeded effectively in this catalytic system.The catalytic system of Pd(OAc)2/EG was successfully extended for ligand-free Suzuki reaction of aryl bromides with arylboronic acids in air at room temperature. Coupling between 4-bromoanisole and phenylboronic acid was selected as a model reaction for screening of the conditions. Under the optimized conditions (0.5 mol% Pd(OAc)2,2 equiv. K3PO4·7H2O,2 mL EG), the Suzuki reaction of a variety of aryl bromides with arylboronic acids could be conducted very fast and afford high isolated yields.