Palladium-Catalyzed Ligand-Free Suzuki Reaction

Two novel and highly efficient catalytic systems of Pd(OAc)2/EtOH/DMA and Pd(OAc)2/i-PrOH(50%) have been developed for the Suzuki reaction. The main contents of this thesis are as follows:1. A highly efficent protocol for the Pd(OAc)2-catalyzed aerobic Suzuki reaction of aryl chlorides was developed. The Suzuki reaction between 4-chloronitrobenzene 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. K2CO3, EtOH/DMA 2:2 mL, 80℃), the couplings of different activated aryl chlorides with aryl boronic acids were completed in 5-60 min using a simple precatalyst Pd(OAc)2 without additional ligand under mild condtions in air, resulting in the highest isolated yield up to 99% and the highest TOF of 2376 h-1. Besides, functional groups such as NO2, CN, CF3, CH3, F, OCH3 and COCH3 were compatible in this catalytic system. Control experiments demonstrate that the high efficiency of this protocol is proposed due to the N,O-bidentate ligand formed in situ via the hydrogen bond of solvents.2. A fast protocol has been developed for the synthesis of N-heterobiaryl compounds by the oxygen-promoted, ligand-free, Pd(OAc)2-catalyzed Suzuki reaction of N-heteroaryl halides in aqueous isopropanol. Initially, the Suzuki reaction between 2-bromopyridine with phenyl boronic acid was chosen as a model reaction for screening of the conditions. Under the optimized conditions (1.5 mol% Pd(OAc)2,2 equiv. K3PO4·7H2O,i-PrOH/H2O 2:2 mL,80℃), cross-couplings of different nitrogen-based heteroaryl halides with various aryl boronic acids proceed smoothly. Because of its high efficiency, the reaction between 5-bromo-2-methoxypyridine with phenyl boronic acid could be carried out smoothly using 0.1 mol% Pd(OAc)2 in 5 min to afford 2-methoxy-5-phenylpyridine in 97% yield with a TOF up to 11640 h-1. Furthermore, the catalytic system is suitable not only for N-heteroaryl bromides, but also for some N-heteroaryl chlorides. The coupling of 2-chloropyrazine with phenyl boronic acid afforded 80% yield in 40 min using 1.0 mol% Pd(OAc)2. A preliminary explanation on the mechanism of the oxygen-promoted Suzuki reaction of N-heteroaryl halides in aqueous was given.3. The catalytic system of Pd(OAc)2/i-PrOH(50%) was successfully extended for the Pd(OAc)2-catalyzed Suzuki reaction of aryl bromides with aryl boronic acids in air at room temperature. Coupling between 4-bromoanisole and phenyl boronic acid was selected as a model reaction for screening of the condions. Under the optimized conditions (0.5 mol% Pd(OAc)2,2 equiv. K2CO3,i-PrOH/H2O 2:2 mL), the Suzuki reaction of a variety of aryl bromides with aryl boronic acids could be conducted very fast and afford high isolated yields. Furthermore, the oxygen can also play a role as a promoter in the Pd(OAc)2-catalyzed ligand-free Suzuki reaction of aryl bromides in air at room temperature in 50% aqueous isopropanol.