Study On Copper-Catalyzed Ullmann Reaction

Copper-catalyzed Ullmann reaction is an important method for the formation of C-C, C-N, C-O, and C-S (Se) bonds. However, its large-scale application for industry is difficult, because traditional Ullmann reaction is generally conducted under harsh reaction conditions, such as high temperature, strong base and stoichiometric amounts of copper reagents. During the past decades, chemists used palladium or nickel as the metal-catalyst to promote Ullmann reaction, which proceeded under considerably milder conditions to construct aryl C-N bond and other C-heteroatom bonds. However, it's impossible to apply this protocol for industry extensively, because both palladium and nickel catalysts are expensive and usually need to use phosphine ligands, which are not easy to prepare, sensitive to air or moisture, and toxic.As an alternative metal-catalyzed protocol, copper-catalyzed Ullmann reaction attracts greater attention again because of the low cost of copper reagents. In recent years, Buchwald and Dawei Ma have made significant contribution in this field. They accomplished the same transformation under mild conditions by combining copper(I) iodide with ligands. Base on the background, the main contents of this dissertation are as following:1. We synthesized N-((1H-benzo[d][1,2,3]triazol-l-yl)(phenyl)methyl)acetamide, 2-(1H-benzoimidazol-2-y1)phenol, and a series of analogous enaminone compounds as candidate ligands. Finally, we found that analogous enaminone compounds might work as good partner of the copper-catalyzed Ullamnn reaction.2. To select the most efficient ligand, the coupling reaction of iodobenzene with imidazole was chosen as the model reaction, and this reaction was carried out at 110℃in the presence of CuI and Cs2CO3 in DMSO under N2 atmosphere for 12 hours. After analyzing the results, we found that (E)-3-(dimethylamino)-1-(2-hydroxyphenyl) prop-2-en-1-one works as the best ligand. 3. To determine the most suitable reaction conditions, different parameters such as the amounts of CuI/L5, solvent, and the nature of the base were optimized on the coupling reaction of iodobenzene with imidazole and Pyrrolidin-2-one. After optimization, the best reaction conditions were 10 mol%CuI,20 mol%ligand, and 2.0 equivalents of Cs2CO3 in MeCN at 82℃under N2 atmosphere for 12 hours.4. We studied CuI-catalyzed N-arylation of both azoles and amides with a variety of aryl halides by using (E)-3-(dimethylamino)-1-(2-hydroxyphenyl) prop-2-en-l-one as the ligand. We found that not only aryl iodides wirh high activity could coupl with azoles and amides successfully, but also both aryl bromines and chlorides could be applied in the coupling reactions efficiently.