| In recent years, transition metal catalyzed or mediated cross-coupling reaction provides an effective method for the construction of carbon-carbon bonds and carbonheteroatom bonds which has been applied to the field of medicine, pesticide, the synthesis of natural products as well as new materials, has gradually become an important tool for synthesis of modern organic chemistry. This research aims for the development of novel, highly efficient, highly selective carbon-carbon, carbon-heteroatom bond formation reactions by using copper salt or silver salt as promoter or catalyst through rational design.The thesis is divided into six chapters as follows:In chapter 1, a general review on the development of cross-coupling reactions participated by copper and silver, and emphasis is paid to the development of copper-mediated auxiliary-assisted C-H bond functionalization reactions.In chapter 2, copper-mediated, chelation-assisted ortho C-H bond nitration of benzoic acid derivatives using sodium nitrite as the source of the nitro group has been developed with the aid of an 8-aminoquinoline directing group. In order to find an optimizated reaction conditions, reaction of benzamide with sodium nitrate was investigated by changing Cu salts, base additives, solvents and temperatures. Selective mono- or dinitration can be achieved by simply tuning the reaction conditions. In addition, the auxiliary can be conveniently removed and recovered. To shed some light on the mechanism of this new transformation, a series of control experiments were conducted. These results clearly indicated that the ortho C-H bond cleavage of benzamide was involved in the rate-determining step of nitration. Although the exact mechanism is still not clear at present, on the basis of the above results and literature reports, a plausible reaction mechanism is proposed.In chapter 3, copper-mediated direct ortho C-H bond sulfonylation of benzoic acid derivatives with sodium sulfinates was achieved by employing an 8-aminoquinoline moiety as the bidentate directing group. In order to find an optimizated reaction conditions, reaction of benzamide with sodium nitrate was investigated using various Cu salts, base additives, solvents and temperatures. Consequently, we decided to set reacting 1 equiv of benzamide(0.3 mmol) with 1 equiv of Cu(OAc)2(0.3 mmol), 2 equiv of sodium sulfinates(0.6 mmol) and 2 equiv of K2CO3(0.6 mmol) in DMF at 80 oC as the standard conditions. A variety of electron-withdrawing and electron-donating substituted benzamides were employed to react with alkyl or phenyl substituted sodium sulfinates forming various aryl sulfones. The intermolecular and intramolecular H/D competition experiment indicated that the ortho C-H bond cleavage benzamide was involved in the rate-determining step of sulfonylation.In chapter 4, a copper-catalyzed, one-pot, three-component reaction of a 1-iodo-2-nitrobenzene with sodium sulfide and an aldehyde was achieved. We found that the reaction only occurs in the acetic acid as a solvent. In addition, We found that when 1,10-phenanthroline was used as a ligand in the reaction, the reaction gave the highest reaction yield. By the reaction of substrate 1-iodo-2-nitrobenzenes with different aldehydes, we found that the reaction worked very well with a wide variety of aldehydes including alkyl substituted aldehydes affording the desired 2-substituted 1,3-benzothiazoles in good yields. To explore the reaction mechanism in detail, we performed several control experiments which showed that the reaction proceed through a 2,2′-disulfanediyldianiline intermediates process.In chapter 5, A new method for the synthesis of 1,2-disubstituted acetylenes via copper-catalyzed Suzuki coupling of organoboronic acids with 1,1-dibromo-1-alkenes has been developed. We found that when an N,O-bidentate ligand 8- hydroxyquinoline was used as a ligand in the reaction, the formation of 1,3-diynes, which are derived from the homocoupling of 1,1-dibromo-1-alkenes, can be almost completely suppressed under these optimized conditions, the yield of the corss-coupling product was raised up to 90%. When we explore the scope and limitation of the reaction and found that numerous substituted 1,1-dibromo-1-alkenes can react smoothly with organoboronic acids to deliver the corresponding acetylenes under these optimized conditions, however, when an alkyl substituted 1,1-dibromo-1-alkenes was used as a coupling partner, the reaction cannot proceed. In addition, two plausible mechanisms for the copper-catalyzed Suzuki coupling reaction of organoboronic acids with 1,1-dibromo-1-alkenes are proposed based on a Cu(I)/Cu(III) cycle.In chapter 6, an efficient method for the synthesis of trifluoromethyl, difluoromethyl and sulfonyl-substituted oxindoles has been developed via silver-catalyzed radical tandem reaction of N-methyl-N-phenyl methylacrylamide. In order to obtain the optimum reaction conditions, numerous reaction were conducted using different catalysts, oxidants, solvents and temperatures. Consequently, we decided to set reacting 1 equiv of N-methyl-N-phenyl methylacrylamide(0.3 mmol) with 3 equiv of CF3SO2Na(0.9 mmol), 0.3 equiv of silver nitrate(0.09 mmol) and 3 equiv of(NH4)2S2O8(0.9 mmol) in t-Bu OH/H2 O at 40 oC and stir in nitrogen atmosphere for 12 hour as the standard conditions. A variety of substituted N-methyl-N-phenyl methylacrylamide were employed to react with CF3SO2 Na forming various CF3 substituted oxindoles. In addition, we found that the difluoromethylated products can be also produced in good yields when Zn(SO2CF2H)2(Baran reagent) was used instead of CF3SO2 Na in this reaction under standard conditions. Moreover, when the Langlois reagent was replaced by arylsulfinic acid sodium salt, aryl sulfonated products were produced. To explore the reaction mechanism in detail, we performed a free radical capture experiment which showed that the reaction proceed through a free radical tandem cyclization reaction process. |
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