Pd-Catalyzed Aqueous Carbonylative Coupling Reactions And Double Carbonylation Reaction

Transition metal-catalyzed cross-coupling reactions are the important research area of organic chemistry, among which the carbonylation reaction is one of the most efficient methods to synthesize the carbonyl compounds. In recent years, there have been numerous studies and reports on carbonylation reactions. However, the vast majority of the work was carried out in organic solvents. Owing to the concept of green chemistry, the development of green and efficient carbonylation reactions is highly desirable. One of the important research directions in green chemistry is to replace the traditional volatile organic solvents with the clean and environmentally friendly media. Water is the most abundantly existing solvent in nature and the use of water as a promising medium has attracted widely attention for reasons of nontoxicity, low cost and environmental concerns. This thesis firstly summarized the development of carbonylative Sonogashira coupling reaction, carbonylative Suzuki coupling reaction and double carbonylation of aryl halides with amines, and then successfully established efficient aqueous catalytic systems for producing α,β-alkynyl ketones, diaryl ketones and a-keto amides by performing these reactions using water as a sole medium.A concept of "thermoregulated phase-transfer catalysis (TRPTC)", which can combine the advantages of homogeneous catalysis for reactivity and heterogeneous catalysis for catalyst recovery, is free from the shortcomings of classical aqueous/organic biphasic catalysis, in which the scope of application is restrained by the water-solubility of the substrate. In this thesis, the carbonylative Sonogashira coupling reaction proceeded smoothly by employing thermoregulated ligand L [Ph2P(CH2CH2O)nCH3 (n≈22)]/PdCl2 as catalyst based on TRPTC using water as a sole medium. This catalytic system showed high catalytic activities for aryl iodides. The corresponding products α,β-alkynyl ketones were obtained in 36-91% yields under the moderate conditions. After the reaction, the products could be separated from the catalytic system easily by decanting, and the catalyst was recovered in water and could be reused up to four runs without significant loss in catalytic activity.The thermoregulated ligand L/Pd(OAc)2 was further extended to the aqueous carbonylative Suzuki coupling reaction. The results indicated that the catalytic system demonstrated high catalytic activity and good functional group tolerance for aryl iodides and bromides, giving the diaryl ketones in highest isolated yield up to 93%. And the catalyst was recovered in water and could be reused eight times. In addition, this catalytic system was also successfully employed for the carbonylative Suzuki coupling of benzyl chlorides with arylboronic acids, providing a new method for the synthesis of diarylethanone.The catalytic performance of the catalysts generated from palladium and MeOPEG-NHC precursor imidazolium salts for the aqueous carbonylative Suzuki coupling reaction by using Co2(CO)8 as a CO source has been investigated. The results indicated that MeOPEG-NHC precursor Ⅱ exhibited the highest catalytic activity for the carbonylative Suzuki coupling of the various aryl iodides and activated aryl bromides with arylboronic acids, providing the diaryl ketones in 62-90% yields.Pd-catalyzed aqueous double carbonylation of aryl iodides with amines was also studied. Various reaction parameters were screened by employing double carbonylation of iodobenzene with diethyl amine as a model reaction. A variety of aryl iodides bearing the electron-donating groups converted well with high selectivity to the desired a-ketoamides in 68-85% yields under moderate reaction conditions (50℃,6 atm of CO) by using MeOPEG-NHC precursor III/Pd(OAc)2 as catalyst and Na2CO3 as base.