Palladium-Catalyzed Ligand-free Sonogashira Reaction And Ullmann Reaction

Transition metal-catalyzed carbon-carbon formation reaction, for example Suzuki, Sonogashira reaction, Ullmann reaction and Kumada reaction, is one of the important reactions in modern organic synthesis. In the past three decades, the palladium-catalyzed carbon-carbon formation reaction played a key role in the synthesis of pharmaceuticals, agrochemicals, natural products and functional materials.Generally, the palladium-catalyzed carbon-carbon formation reaction was performed in the presence of ligands. To date, various ligands indeed promote the development of carbon-carbon formation reaction, especially in the activation of inactivated aryl bromides or aryl cholorides. However, organic ligands such as phosphines as well as N-heterocyclic carbenes are difficult to synthesize and/or are sensitive to air or moisture, restricting the reaction to proceed only under inert atmosphere. Recently, the palladium-catalyzed ligand-free system attracts attention due to its simpleness and high efficiency. In the basis of above concerns, this thesis reports two protocols for the palladium-catalyzed ligand-free and aqueous Sonogashira reaction and the Pd/C-catalyzed ligand-free Ullmann reaction in ethylene glycol.1. A ligand-free, simple, highly efficient protocol for Sonogahsira coupling has been developed under air in aqueous media. The Sonogashria reaction could proceed smoothly in the absence of a ligand and copper salts. The optimal reaction conditions were screened using the coupling of4-iodoanisole with phenylacetylene as the model reaction (Pd2(dba)3(0.5mol%), K3PO4·7H2O (2equiv.), EtOH/H2O (3/1, in volume),80℃, under air). The coupling of aryl iodides with aromatic terminal alkynes provided good to excellent yields and moderate to good yields were achieved using aliphatic terminal alkynes as one of the coupling partners. The highest isolated yield was96%. Aryl iodides bearing electron-withdrawing groups were coupled more efficiently than those bearing electron-donating groups.2. A simple, ligand-free protocol for the homocoupling of aryl halides in ethylene glycol has been developed using Pd/C (palladium on carbon) as the catalyst in ethylene glycol. For an effort to examine the feasibility of this catalytic system, the homocoupling of4-bromobenzonitrile was selected as the model reaction to investigate the effect of solvents, catalyst, base and temperature on this reaction. Through screening different conditions, the optimized reaction conditions were obtained (5%d/C (2mol%), K3PO4·7H2O (2equiv.), ethylene glycol (1mL),80℃).A series of substituted aryl halides carried out this reaction under the above optimized reaction conditions. The results showed that not only aryl iodides and aryl bromides but also aryl chlorides could conduct the Ullmann reaction smoothly. Noticeably, the electron effect and steric effect on this coupling were obvious. Moreover, the reaction could proceed without additive reductant.