Copper-catalyzed Oxidative C-C Bond Cleavage Of Unstrained Ketones

In theory, the carbon-carbon bond cleavage reaction can not only achieve the carbon skeleton of the molecule to rebuild, but also introduce two different functional groups, making it employing simple starting materials, traditional methods difficult to build efficient synthesis of a molecule or the product with functional groups, thereby imparting synthetic strategy more flexibility to provide a new approach to the synthesis of reference applications. Because of this, in recent years, the carbon-carbon bond cleavage as a novel synthetic strategy, aroused widespread interest. Carbonyl functional group is common, widely present in the molecular structure of the compound. Although studies on ortho carbonyl carbon-carbon bond cleavage were fully developed, but most of them were based on this strategy to cleave the carbon-carbon bond in a four-membered ring strained ketone, and research for unstrained of five or six-membered ring ketone was less reported and which is more challenging. This thesis conducted the research of copper-catalyzed oxidative cleavage of the unstrained cyclic ketones with air generating amides with aldehyde.Research work of this thesis includes the following four parts:The first part, with 2-tetralone and aniline as a starting material, a copper catalyst, acetonitrile as the solvent, under atmospheric conditions, via column chromatography to give the desired product, which is few. Then to the reaction conditions do screening, including raw material ratio, catalyst, ligand, temperature, solvent, etc., and finally 10 mol% CuCl2·2H2O / 20 mol% 1,10-Phenanthroline monohydrate as a catalyst system, CHCN / dioxane as a solvent mixture, temperature 40 degrees, to obtain 71% of the desired product under atmospheric conditions.The second part of the scope of the substrate has been actively explored. Making use of the optimist conditions, both alkylamine and arylamine can be better reacted to afford the desired products. Then, we synthesized various substituted 2-tetralone to study feasibility in this reaction, the results in the production was medium to high yields compatible with an electron withdrawing group and electron donating group.The third part, we throwed a detailed study to the reaction mechanism. First synthesized possible intermediates and tested them, then comprehensive isotope experiments, as well as control experiment have been carefully conducted.The last part was what characterized the product of different structures, including IR and 1H NMR, 13 C NMR, melting point, high-resolution mass spectrometry and some other data.In conclusion, this paper developed a new strategy of copper-catalyzed aerobic oxidative C-C bond cleavage of unstrained ketones with air and amines, which is full of innovation, provide a new method for the construction of the carbon skeleton, enriched carbon-carbon bond cleavage methodology greatly, establish a theoretical basis and reference for the experimental drug synthesis.