Catalyzed Carbo Key Coupling. Cu (¢ñ) And Its Application In The Synthesis Of Heterocyclic Compounds

During the last 10 years, with the development of the catalysis system which intergrading ligands with catalyst, Copper-catalyzed Ullmann type cross-coupling reactions came to a new age. The foundation of C-C,C-N,C-O,C-S bond could carry out with fewer copper-catalyzed in mild conditions. Copper-catalyzed Ullmann type cross-coupling reactions also have been used in synthesizing heterocycles as pyrrole, imidazole,benzimidazole,benzofuran,indole etc. and even in synthesizing nature compounds. In this dissertation, we emphasized on the application of ligand and ortho-substituent promoted copper catalyzed Ullmann type reactions. We studied some tandem processes in which Ullmann reactions participated of preparing pharmicactive heterocycles.In the second chapter of this dissertation, we developed a high effective, atom economic one-pot procedure of preparing substituted 1H-benzimidazoles and 1,3-dihydrobenz-imidazol-2-ones in mild condition. We initiated our studies by screening suitable conditions for coupling aqueous ammonia with 2-iodophenyl-benzamide. After screened different ligands, base, solvent and their dosage, we obtained the optimized coupling reaction conditions:10 mmol% CuⅠ,20 mmol% L-Proline,1.5 eq. NaOH,1.5 eq. aqueous ammonia, rt. After the coupling reaction, AcOH was added into the reaction mixture at 50℃, and We were pleased to find that the desired 2-phenyl-benzimidazole was isolated in 83% yield. And the process was suitable in a large scope. Then we moved our attention to synthesize 1,3-dihydrobenzimidazol-2-ones via coupling 2-iodophenyl-carbamates with aqueous ammonia. We found that the coupling step proceeded smoothly at room temperature, and the resultant amines were in situ converted into 1,3-dihydrobenzimidazol-2-ones by heating at 130℃.In the third chapter of this dissertation, we developed a copper-catalyzed, ligand and ortho-subsituent promoted procedure of preparing substituted 5H-dibenzo[b,e]-[1,4]diazepin-11(10H)-ones. We initiated our studies by screening suitable conditions for coupling 2-bromo-N-phenylbenzamide with BnNH2. Surprisingly we found the ortho-subsituent groups CONHR could strongly promoted the coupling reaction. Without any ligand, the coupling reaction could carry out in room temperature, with only 1 mmol% CuCl as catalysis, 1eq. K3PO4 as base, 1mL DMF as solvent. Then we examined the scope and limitation of the promotion of the ortho-subsituent groups. We found that coupling 2-bromo-N-phenylbenzamide with primary amine and ring-like secondary amine could be promoted by the ortho-subsituent groups CONHR, but when the 2-bromo-N-phenylbenzamide was substituted by electron-withdrawing groups, the ortho-subsituent promotion deactivated. Then we tried to couple 2-chloro-N-phenylbenzamide with amine and found that with 20 mmol% N,N-dimethyl glycine the coupling reaction could carry out at 60℃. In summary, we developed a new ortho-subsituent promoted groups CONHR after two known ortho-subsituent promoted groups COOH and NHCOR. At last, by copper catalyzing, ligand and ortho-subsituent promoting, we successfully synthesized substituted 5H-dibenzo[b,e]-[1,4]diazepin-11(10H)-ones in one step at room temperature.