Palladium-Catalyzed Cyclization Of 2-Ethynyl Azides And Suzuki Cross-Coupling Reaction

Both the intramolecular cyclization and the cross-coupling reactions are important protocols for the construction of carbon-carbon bonds. Particularly, azides compounds are important organic blocks for the synthesis of nature products, biologically active organic moleculars and organic functional materials. The dissertation includes two contents:(Ⅰ) the halopalladation and thiopalladation reactions of 2-alkynyl benzyl azides; (Ⅱ) palladium-catalyzed Suzuki cross-coupling reaction using pyrimidone as ligand.(1) A selective halopalladation annulation protocol for the synthesis of halo-substituted heterocycles is developed.4-Haloisoquinolines and 3-haloindoles can be selectively synthesized by judicious choice of 2-alkynyl azides and the reaction conditions. In the presence of PdX2 (X Br, Cl) and halide sources, a variety of 2-alkynyl benzyl azides or 2-alkynyl aryl azides smoothly underwent the halopalladation cyclization to afford the corresponding 3-substituted 4-haloisoquinolines and 2-substituted 3-haloindoles in moderate to good yields. Importantly, a halide was introduced into the products among the halopalladation annulation of 2-alkynyl azides, which makes the methodology more attractive for organic svnthesis.(2) A novel and selective method for the synthesis of isoquinolinones by palladium-catalyzed annulations of 2-alkynyl benzyl azides is presented. In the presence of PdBr2, CuBr2 and CH2C1CH2C1,3-substituted 4-bromo isoquinoline-1(2H)-ones are prepared in moderate to good yields. It is noted that HO Ac can promote the reaction leading to 3-substituted 4-bromoisoquinoline-1(2H)-ones. Electron-withdrawing groups on the aromatic ring at the terminal alkynes favoured the desired reaction, but the electron-donating groups displayed less activity.(3) Synthesis of 4-sulfenylisoquinolines via palladium-promomted annulation reactions of 2-alkynylphenylazides with disulfides and iodide is described. The key of the reaction is generation of RSI in situ from the reaction of RSSR with I2. In the presence of I2 and Pdl2,4-sulfenyl isoquinolines are selectively prepared from the cyclization of 2-alkynyl benzylazides with disulfides in moderate to excellent yields.(4) Efficient palladium-catalyzed Suzuki cross coupling reaction promoted by pyrimidone has been developed. The Pd(OAc)2/oritic acid catalysis system displays exceptionally activity and extended the scope to a various aryl halides, including less active aryl chlorides and vinyl bromides. It is noteworthy that the reactions between (E)-alkenyl bromides and (E)-bromo-substituted styrenes are carried out smoothly to afford stilbene derivatives in excellent yields.