Synthesis Of Multi-Substituted Pyrroles Via Cu-Catalyzed Ullmann Coupling Reaction And Ag-Catalyzed Chlorination Of Aromatic Compounds

In modern organic synthesis, it has been become an important, useful and efficient method for the transition metal-catalyzed C-C or C-X (X=O, N, S, etc.) bond formation in the last few decades. Copper-catalyzed modern Ullmann Reaction have been well developed to be performed under mild conditions. While Cu-catalyzed chemistry has been studied extensively for decades, utilization of silver in organic synthesis has been broadened due to its low toxicity. In this dissertation, first, the synthesis of poly-substituted pyrroles via Cu-catalyzed intermolecular Ullmann reaction coupling was first investigated. Second, the Ag-catalyzed chlorination of aromatic compounds was studied on basis of our group's work in silver-catalyzed decarboxylation reactions. It could be described as the following two parts:1. We first explored the feasibility of the C-vinylation of activated methylene with N-(2-bromoallyl)aniline and 1,3-diketone compound ethyl 3-oxobutanoate under Ullmann reaction conditions. Employing 20 mol% CuI as catalyst,40 mol% quinolin-8-ol as ligand,2 equivalents of CS2CO3 as base, at the temperature of 80℃in MeCN, as the optimized reaction conditions, we have successfully got the compound of 1,2,3,4-substituted pyrrole. The reaction mechanism was then discussed which involves the C-C vinylation coupling of activated methylene followed by condensation of aniline with the carbonyl and the subsequent isomerization of the double bond.2. The two-type amine-compounds,N-phenylacetamide and 2-phenylpyridine, were selected as the substrates for the Ag-catalyzed chlorination reaction. Employing 10 mol% AgOTf (AgOTf=(trifluoromethylsulfonyloxy)silver),2.5 equivalents tert-butyl hypochlotite as oxidant, at refluxing temperature in acetonitrile, as the optimized reaction conditions, the chloro-substituted compounds were achieved. In the reaction of N-phenylacetamide with t-BuOCl, the catalyst was the AgOTf, and the temperature was room temperature; and the other was AgOTf-complex and 80℃. We also found that the reaction was retarded by the generation of undesired AgCl, which makes the transformation of lower efficiency.