Research On The Application Of ?-Imino Gold Carbenes In The Synthesis Of Nitrogen-containing Heterocycles

Gold-catalyzed tandem reactions for the systhesis of bioactive nitrogen-containing heterocycles and natural products is one of the most important and popular research fields in modern organic chemistry. However, the report about the synthesis of nitrogen-containing heterocycles via ?-imino gold carbenes is relatively few. To expand the application of ?-imino gold carbenes generated by gold-catalyzed reactions, we plan to design new alkynyl arylazides with novel structures for the synthesis of nitrogen-containing heterocycles and natural products.In this thesis, carboxylic acids, alkynes, oxygen-containing heterocycles and aldehydes were used as the nucleophiles. The main part of this thesis is divided into four parts:Part I : The ~1H-indol-3-yl acetates were efficiently prepared via ?-imino gold carbenes generated by gold-catalyzed reactions of 2-alkynyl arylazides. A very simple and general method for the synthesis of ~1H-indol-3-yl acetates was provided after examining the substrates scope. The desired products were afforded up to 80% yield at 60 oC for 0.75 h with 2 mol%JohnPhosAuCl as catalyst. And carboxylic acids were used as both nucleophiles and solvents.Part II : 3-Alkynyl indoles were efficiently prepared through trapping of ?-imine gold carbenes by alkynes, generated by gold-catalyzed tandem reactions of 2-alkynyl arylazides. A very simple and general synthetic method for the efficient synthesis of 3-alkynyl indoles was provided. The desired products were afforded up to 92% yield at 60 oC for 1.3 h with 2 mol%JohnPhosAuCl as catalyst. And alkynes were used as both nucleophiles and solvents.Part III : A novel method for the formation of indole derivatives via gold-catalyzed tandem reactions of 2-alkynyl arylazides and oxygen-containing heterocycles has been developed.Experimentals revealed treating a solution of reaction containing 2-alkynyl arylazides(1equiv) and 1,4-dioxane(0.5 mL) with 2 mol% t BuXPhosAuNTf2 in the presence of 3equivenents of MsOH at 60 °C for 1 h gave the best result. Under these conditions,2-(2-((2-phenyl-~1H-indol-3-yl)oxy)ethoxy)ethyl methanesulfonate was obtained in 95%yield.Part IV : A novel and efficient method to prepare 6-(2-azidophenyl)-4H-1,3-dioxines and4,5-dihydro-[1,3]dioxino[5,4-b]indoles by gold-catalyzed tandem annulation of3-(2-azidophenyl)prop-2-yn-1-ols with aldehydes is described. The reactions were accomplished in moderate to excellent yields under mild reaction conditions. Uniquely, the reactions were found to perform with complete control of product chemoselectivity for a variety of 3-(2-azidophenyl)prop-2-yn-1-ols in the presence of XPhosAuNTf2. Experimentals revealed treating a solution of reaction containing 2-alkynyl arylazides(1 equiv) and propionaldehyde(10 equiv) with 2 mol% XPhosAuNTf2 at 0 °C for 1 h gave the best result. In the work, DCEwas used as solvent. Under these conditions,2-(2-((2-phenyl-~1H-indol-3-yl)oxy)ethoxy)ethyl methanesulfonate was obtained in 68%yield.Research on the synthesis of nitrogen-containing heterocycles via ?-imino gold carbenes would contribute to development of organic chemistry, especially the gold-catalyzed chemistry.