Oxidative C-C Bond Forming Reaction Between Alkyl Amines And 1,3-dicarbonyl Compounds

Carbon-carbon bond forming reactions are the core transformations in the field of organic synthesis. Transition metals mediated C-C bonds forming is one of the most commonly and effective methods. While some traditional methods often requires complex materials, tedious procedures, harsh reaction conditions and so on, which does not meet the requirements of green chemistry. Cross-Dehydrogenative-Coupling Reaction can activate C-H bonds directly by using metal catalysts, which shortens the reaction process and reduces the consumption of raw materials. Nowadays, CDC Reaction has becoming a new and efficient strategy to build C-C bonds and has made rapid developments and gained widely application. However, in view of green chemistry and sustainable development point, green and recoverable regents would be more desirable. Iodide and its relevant compounds have received more and more attention in C-H activation, C-O and C-N construction for its cheap and environmental friendly characteristics; however, few results about C-C bond formation were reported.In addition, the oxidative coupling reaction of aromatic amines is popular in many chemists and has been widely studied, while no words about the oxidative coupling of aliphatic tertiary amine with less reactivity. Morever, multi-component tandem reaction is also ideal for the construction of multiple chemical bonds because of its economy in reaction steps.We used the green catalyst system, tetra-n-butylammonium iodide and tert-butyl hydroperoxide, to realize the CDC reaction about N-ethyl aliphatic tertiary amine and 1,3-dicarbonyl compounds for the first time, and gained a series of methylene-bridged bis-1,3-dicarbonyl compounds. This green and environmental friendly transformation could not only operate simply but also has a broad substrate scope. What’s more, the β-carbon of DIPEA was converted to the methylene carbon through an oxidative C-C bond cleavage. We believe this C-C bond cleavage of tertiary aliphatic amine holds promise to develop other novel transformations.Using tert-butyl hydroperoxide as the oxidant and without any catalyst, we developed a method to construct the asymmetric 1,5-diketone compounds through the three-compound addition reaction between β-ketoesters substrates, trifluoromethyl-β-diketones and methylamines, strategically using the cleavage of trifluoroacetyl. This domino reaction is clean and simple operation. Moreover, the scope of substrates is very wide, and various of substituted β-ketoesters substrates and trifluoromethyl-β-diketones both are well suitable for this reaction. Besides, it has overcome the traditional method’s shortcomings, such as expensive reagents, harsh conditions and so on. This coupling reaction including cleavage and formation of different kinds of C-C bonds and C-N bonds would be a valuable improvement of metal-catalyzed CDC reaction. The yields in preparing the symmetry 1,5-diketones is lower, which needs further study in our laboratory.This study achieved a mild and clean oxidation coupling strategy to construct multiple C-C bonds, untilizing aliphatic tertiary amine as carbon source, developed a domino reaction including Oxidation-Mannich reaction-Cope elimination-Micheal addition-Trifluoroacetyl leaving, and then explored the mechanism profitably. All of this study will have a great guiding significance for the development and application of aliphatic tertiary in organic synthesis in future.