Palladium-Catalyzed Ligand-Free And Aqueous Suzuki Reaction

Transition metal-catalyzed cross-coupling reactions such as Heck reaction, Stille reaction, Negishi reaction and Kumada reaction, are indispensable tools in modern organic synthesis. Due to the mild reaction conditions, low toxicity associated with boron compounds and broad functional groups tolerance,the palladium-catalyzed Suzuki reaction has received great attention and been widely used in the synthesis of natural products,pharmaceuticals and advanced functional materials.Green chemistry turns into a hot and edge field in current chemistry research. In recent years, the use of water as a reaction solvent or co-solvent has received much attention in synthetic organic chemistry because of many potential advantages such as cost, safety, and environmental concern. In this thesis, we systematically investigated the palladium-catalyzed ligand-free aqueous protocols for Suzuki reaction and preliminarily examined the effect of water and atmospheres on the Suzuki reaction. The main contents are as follows:1. A mild and effective PdCl2-H2O/DMF (N,N-dimethylformamide) protocol for the Suzuki cross-coupling reactions of aryl bromides with arylboronic acids under air at room temperature was developed. Under the optimized conditions (PdCl2 0.5 mol%, K2CO32 equiv., 50 vol% aqueous DMF, room temperature), the couplings of different aryl bromides with arylboronic acids were completed in short times, resulting in the highest isolated yield up to 99% and the highest TOF of 4000 h-1. It is noteworthy that various functional groups such as 4-OCH3,4-CN,4-COCH3,4-F,2-CH3,2-OCH3, could be tolerated under the optimized conditions. Steric effect and electronic effect only made a little impact on the reaction rate. Moreover, this aqueous system could be extended to the cross-couplings of nitrogen-based heteroaryl bromides with arylboronic acids. The coupling of 2-bromopyridine with phenylboronic acid afforded 81% yield in 12 h in the presence of K3PO4·7H2O and 1.5 mol% PdCl2 at room temperature.2. A fast, convenient and ligand-free protocol for synthesizing a series of 4-aryl-substituted triphenylamine derivatives is described by the Pd(OAc)2-catalyzed aerobic Suzuki reaction of aryl halides with 4-(diphenylamino)phenylboronic acid in aqueous i-PrOH. Initially, the coupling of 4-bromobenzonitrile with 4-(diphenylamino)phenylboronic acid was chosen as a model reaction for screening of the conditions. Under the optimized conditions (0.5 mol% Pd(OAc)2,2 equiv.K3PO4·7H2O,i-PrOH/H2O 1.35:0.65 mL), aryl bromides bearing both electron-withdrawing groups and moderate electron-donating groups such as methyl, methoxy, cyano and acetyl, provided the corresponding products in 75-98% yields within 25 min at room temperature.As for the aryl bromides containing strong electron-donating groups such as OH,NH2, good to excellent yields could also be obtained at 50℃.In addition, after further optmizing reaction conditions (1.5 mol% Pd(OAc)2,2 equiv.K3PO4·7H2O, i-PrOH/H2O 1.35:0.65 mL,80℃),a wide range of substrates including heteroaryl halides could perform the Suzuki reaction with 4-(diphenylamino)phenylboronic acid smoothly, providing the corresponding 4-heteroaryl-substituted triphenylamine derivatives in the yields of 46-99%.3.A systematical investigation on the effect of water and different atmospheres on the reactivity of the palladium-catalyzed Suzuki reaction has been carried out. The results show that water and atmosphere have a synergistic effect on the reaction. An aerobic atmosphere demonstrates a positive effect on the reactivity of the Suzuki reaction in an aqueous media and a negative effect in a pure organic solvent, which exhibits that the water plays a crucial role for the function of the atmosphere on the palladium-catalyzed ligand-free Suzuki reaction. Besides, the synergistic effect is universal in aqueous media.