Construction Of Nitrogen-containing Compounds Via Tandem Reactions

N-containing compounds, which are always found in many natural products and medicines commercially available, are very important object of deep investigation due to their broad ranges of promising bio-activities. According to the statistical data on top 200 medicinal sales in America in 2009, about 80 percent is N-containing architectures. It’s generally accepted that tandem reaction is one of powerful and green tools to construct the desired products with molecular diversities and structural complexation using readily available substrates as starting materials. In this regard, tandem reaction provides us a fast and efficient access to the libraries of natural product-like compounds.Compounds containing isoquinoline and sulfonamide skeleton generally have remarkable bio-activities. Develop some tandem reactions for efficient and quick generation of diverse natural product-like molecules with these privileged skeleton, which can construct corresponding small molecular libraries with structural diversity and molecular complexation for further High-Throughput Screening(HTS) in the drug discovery process. Based on this, this thesis is mainly focused on following sections.Firstly, we have developed a highly efficient, novel and straightforward synthetic protocol for the construction of 4-carboxylated isoquinolines through a Ag(I) and Cu(I) co-catalyzed one-pot reaction of 2-alkynylbenzaldoxime and aldehyde or alcohol in the presence of KI and TBHP under mild conditions starting from easily available materials. The reaction enriches the tool box for the preparation of esters.Secondly, we have developed an efficient and novel AgOTf and Cu(OAc)2 co-catalyzed tandem reaction of 2-alkynylbenzaldoxime with ether, which gives rise to C-1 alkylation isoquinoline derivatives in moderate to good yields.Thirdly, we have described a silver(I)-catalyzed reaction of 2-alkynylaryl aldimine with trimethyl(trifluoromethyl)silane for the synthesis of 1-(trifluoromethyl)-1,2-dihydroisoquinolines. This transformation proceeds efficiently under extremely mild conditions to generate the corresponding products in good yields. A three-component reaction of 2-alkynylbenzaldehyde, amine, with trimethyl(trifluoromethyl)silane is presented as well. The broad reaction scope is demonstrated and the diversity could be easily introduced.Fourly, we have developed a facile approach to the synthesis of 1-phosphorylated isoquinolins starting from readily accessible 2-alkynylbenzaldoxime and commercially available H-phosphine oxides, and H-phosphinate esters. The reaction proceeds smoothly to provide the corresponding products in moderate to excellent yields. This methodology will serve as an important tool for the efficient synthesis of a variety of useful 1-phosphonylated isoquinolines.Fifth, we have discovered a copper-catalyzed three-component reaction of triethoxysilanes, sulfur dioxide and hydrazines, leading to N-aminosulfonamides in moderate to good yields. Not only triethoxy(aryl)silanes but also triethoxy(alkyl)silanes are compatible during the process of insertion of sulfur dioxide. Additionally, diethoxydiarylsilanes are suitable under the conditions as well. This method provides an excellent alternative to N-aminosulfonamides.