Synthesis Of N-Heterocyclic Compounds By Transition Metal Silver And Copper And Related Mechanistic Investigations

Synthesis of heterocyclic compounds with high efficiency, selectivity, and yield under mild reaction conditions is a core objective of modern organic synthesis. Heterocyclic compounds by far the largest of the classical divisions of organic chemistry, which are the basic constituents of numerous natural products, biologically active alkaloids, pharmaceuticals, and agrochemicals. The development of heterocyclic compounds depends on the construction of carbon-carbon and carbon-heteroatom bond.In the chemical synthesis industry, people always tend to use traditional and conventional synthetic methods to build heterocyclic compounds. The reason may be that these conventional reactions are more reliable and easy to control. However, these types of reactions are often accompanied by a large amount of wasted byproducts and lower yields. In the last four decades, the transition-metal-catalyzed coupling reaction has become one of most effective way to construct the carbon-carbon and carbon-heteroatom bond. Heterocyclic chemistry gets its full evolution and development with the rapid development of organometallic chemistry. Transition-metal-catalyzed reactions have become the most attractive methodologies for synthesizing heterocyclic compounds, since a transition-metal catalyzed reaction can directly construct complicated molecules from readily accessible starting materials under mild conditions. These new and efficient synthetic transformations have also gradually been applied in practical industrial production.(1) A silver-catalyzed click synthesis of pyrroles by the co-cyclization of terminal alkynes and isocyanides has been demonstrated. From a synthetic point of view, this protocol represents an extremely simple, efficient, and atomeconomic way to construct substituted pyrroles in good yields with high selectivity, thus complementing the click method for the rapid formation of multifunctional heterocycles.(2) A novel copper and silver synergistically catalyzed C-C/C-N oxidative cross-coupling/cyclization between2-pyridinyl-?-ketone derivatives and alkynoates has demonstrated. This approach provides an efficient way to construct heteroaromatic indolizine derivatives in good yield with high selectivity from basic chemical materials. Various2-pyridinyl-?-ketone derivatives could react smoothly with both internal and terminal alkynes. Preliminary mechanistic studies by using in situ IR supported the2-pyridinyl-?-ketones were activated by Copper salts, on the other hand, the sliver salts not only played a role as the oxidant, but also acted as the Lewis acid to activate the alkynoates. The structure of copper complex was also unequivocally established by the X-ray single-crystal analysis.(3) A novel reagent-free oxidative cyclization between a-picoline derivatives and nitroolefins has been developed. This approach provides an extremely simple, efficient and atom-economic way to construct heteroaromatic indolizine derivatives. In this process, the nitro group acts as an internal oxidant. Based on the mass spectrometer (MS) and the gas chromatography (GC), the generations of the nitroxyl in this oxidative transformation were proved.