Palladium Catalyzed Carbon-Carbon Bond Formation:From Flask To Microfluidic Channel

Transition metal catalyzed coupling reactions are one of the most important processes in organic synthesis chemistry. As a powerful and popular method for the formation of carbon-carbon bonds, it has been extensively studied. Due to their advantages, such as mild reaction conditions, wide substrate scopes, good functional group tolerance, easy separation of product and excellent selectivity, transition metal catalyzed cross-coupling reactions have been widely applied in various fields of organic chemistry, including the synthesis of nature products, bioactive molecules, pharmaceutics, optic materials, molecular devices and organic polymers. Accordingly, development of novel catalytic system with high efficiency and selectivity for the formation of carbon-carbon bond is still of great significance. This dissertation mainly focused on palladium catalyzed carbon-carbon bond formation reactions, from homogenous to that immobilized in microfluidic channels, which consists of the following five parts:1. The transition metal catalyzed carbonylative Suzuki cross-coupling reaction, homocoupling reaction of terminal alkynes, Suzuki cross-coupling reaction as well as the cross-coupling of haloalkynes with terminal alkynes were reviewed. The research progresses on the application of microfluidic technology in the carbon-carbon bond formation reactions were also briefly introduced.2. The carbonylative Suzuki cross-coupling reactions of boronic acids with aryl iodides catalyzed by Pd2(dba)3 as a ligand-free catalyst under atmospheric pressure of carbon monoxide has been firstly developed. Under mild reaction conditions, a broad range of aryl/heteroaryl iodides and aryl/heteroaryl boronic acids were selectively coupled to afford the corresponding diaryl ketones in good to excellent yields (63 to 98%) at low catalyst loadings (0.05 to 2 mol%). Moreover, the catalyst can be recycled.3. A mesoporous silica SBA-15 supported palladium with spindle-like nitrogen donor groups, 1,4-diaza-bicyclo[2.2.2]octane, has been successfully prepared. The catalyst was systematically characterized by elemental analysis, X-ray photoelectron spectroscopy, high-resolution transmission electron microscope, nitrogen physical adsorption, Brunauer-Emmett-Teller method and X-ray powder diffraction. The analyses indicated that the mesoporous structure of the materials was retained during the immobilization process.4. The amine-functionalized mesoporous silica SBA-15 supported palladium catalyst was applied for homocoupling of terminal alkynes and exhibited very high activity for terminal alkynes carrying various substitution groups, yields ranging from 70% to 94%, with a significant advantage that air acted as the oxidant. It also showed good reusability, could be easily recovered through filtration and washing, and reused at least five times with virtually no evident loss of catalytic performance. For the first time, this supported palladium has been used as an efficient phosphine-free and reusable catalyst for the cross-coupling of haloalkynes with terminal alkynes. A variety of haloalkynes and aromatic/aliphatic terminal alkynes were selectively coupled to afford unsymmetrical 1,3-diynes in good yields. Furthermore, it was also proved to be an effective and air-stable heterogeneous catalyst for Suzuki coupling of aryl halides (X= I, Br) with arylboronic acids.5. A practical open channel microfluidic reactor with immobilized palladium complex was built on a cyclic olefin copolymer (COC) chip that was fabricated with a very simple hot-embossing technique. Palladium complex was immobilized on a photochemically grafted layer of polymerized N-[3-(dimethylamino)propyl]methacrylamide. Surface modification and catalyst immobilization onto COC were systematically characterized with streaming potential, surface contact angle, attenuated total reflection Fourier transform infrared spectrometry, scanning electron microscopy, atomic force microscopy and X-ray photoelectron spectroscopy. The reactor was comprised of a single 15 cm long serpentine channel of 120μm(i.d.) and exhibited high efficiency for the Suzuki cross-coupling reaction of aryl iodides and bromides with arylboronic acids, affording good to excellent yields of the corresponding products. Compared with the traditional reaction system, the reactions could be carried out smoothly with reduced reaction time and lower reactant consumption in the microreactor. The proposed system may have great potential for highthroughput screening of catalysts and reaction conditions.