Copper-Catalyzed Oxidative Coupling Reactions Of Ketones Or Acids And Annulation Of Isochromenes

The oxidative coupling reaction includes the oxidative cleavage of chemical bonds by oxidants, followed by functionalization to construct various chemical bonds, such as new carbon-carbon bonds and carbon-heteroatom bonds. The oxidative coupling reactions are generally used to cleave the carbon-carbon bonds and carbon-heteroatom bonds under neutral reaction conditions. Particularly, the oxidative coupling reactions through the carbon-hydrogen bond cleavage are the hot-topic in organic synthesis because they do not need per-functionalization substrates with high atom-economy and benign-environment. For these reasons, the utilizations of the oxidative coupling reactions in the synthesis of natual products and lead drug frameworks are high desirable.Copper catalysts, expensive catalysts, are widely used in organic synthesis. Recently, copper-catalyzed oxidative coupling reactions have been one of the the most important and challenging areas in organic synthesis. Among these reactions, the key is how to improve the catalytic activities of copper catalysts.The dissertation mainly studies on the copper-catalyzed oxidative coupling reactions of ketones or acids and annulation of isochromenes. The contents of this dissertation are as following:(1) Recent progress in the copper-catalyzed oxidative coupling reactions has been described in detail. Three parts on the construction of chemical bonds are discussed in this chapter, including:(i) Advances in the construction of the carbon-carbon bonds by copper-catalyzed oxidative coupling reactions,(ii) advances in the construction of the carbon-nitrogen bonds by copper-catalyzed oxidative coupling reactions, and (iii) advances in the construction of the carbon-oxygen bonds and the other chemical bonds by copper-catalyzed oxidative coupling reactions. We focus on the results and the mechanisms of the copper-catalyzed oxidative coupling reactions.(2) An efficient copper-catalyzed α-aminoxylation of ketones with TEMPO was presented for the synthesis of2-aryloxy-1-aryl-2-(2,2,6,6-tetramethylpiperidin-1-yloxy)ethanones, fundamental structural units that are found in natural products and pharmaceutical agents, in moderate to excellent yields. It is noteworthy that the Cu/Fe catalyst can be recovered and reusable several times with highly catalytic activity, and this method is the first example for the Cu-catalyzed oxyamination reaction of ketones with TEMPO. Importantly, the products,2-aryloxy-1-aryl-2-(2,2,6,6-tetramethyl-piperidin-1-yloxy)ethanones, can readily deliver aryl glyoxylates, which play an important role in biological processes as useful intermediates in the synthesis of some natural products, such as the3-deoxy-2-ulosonic acids and their derivatives.(3) A new, general copper-catalyzed amidation of acids with formamides or acetamide to selective synthesize new amides with the aid of DAB CO ligand and TBHP oxidation is presented. This method has high compatibility with a wide range of acids, including alkyl acids, aryl acids, α,β-unsaturated acids and amino acids. Importantly, this method allows the use of various formamides and an acetamide as the amine resources for amidation with acids leading to new amide products, which open a new door to use acids for the direct synthesis of amides, a class of fundamental chemicals in organic synthesis and chemical industries.(4) A novel Lewis acid-catalyzed annulation reaction has been established for the synthesis of benzocyclohepta[b]indoles. This method represents a new annulation strategy to a seven-membered carbocyclic ring system from two3-(1H-isochromen-1-yl)-1H-indole molecules using Cu(OTf)2catalyst; moreover, the products, benzocyclohepta[b]indoles, can be used as the rapid mercuric ion colorimetric detection reagents.(5) Sulfones are important units found in organic materials, bioactive molecules and pharmaceuticals, as well as widely serve as valuable intermediates in synthetic chemistry. A new, simple base-mediated nucleophilic replacement reaction of1,2-bis(phenylsulfonyl)ethane with ketones has been developed for the synthesis of1-aryl-4-(phenylsulfonyl)butan-1-ones. This method represents the first example of preparing new functionalized sulfones using commercial available1,2-bis(phenylsulfonyl)ethane instead of vinyl sulfones as the sulfone resource, and expands the scope to common ketones.