Selective C-N Bond Formation Of Arylhalides And Halogenated N-heterocyclic Arenes

N-arylheteroarenes is of growing interest for pharmaceutical synthesis, organometallic catalysis, advanced materials application, and the field of dye-sensitized solar battery. A method for the accurate control of the C-N bond formation was development, which can control of the selectivity of the pyridine ring or an aromatic ring of two or more halogen atoms by screening of the catalytic system. This paper includes the following four sections:1. A practical and efficient protocol for synthesis of 2-bromo-6-substituent-pyridine compounds via copper-catalyzed selective C-N bond formation reaction of 2, 6-dibromopyridine with amines has been developed. The major advantage for this protocol is that the selectivity of the bromide atom on pyridine ring for C-N cross-coupling could be completely controlled. Therefore, a novel series of the unsymmetrical pyridine-bridged 2,6-di-substituents compounds were initially synthesized in two steps through a selective copper-catalyzed coupling reaction.2. To overcome the disadvantage of the trantional pyridine-bridged pincer ligands, a metal-free method for highly site-selective C-N bond-forming reaction of polyhalogenated pyridines and pyrimidines by using 2, 6-difluoro-pyridine, which is simple and commercially available, was developed. In particular 5-fluoro-2-chloropyridine selective activation of C-F bond coupling reaction with N-heterocyclic amines under the system, conversely 5-fluoro-2-chloropyrimidine selective activation of C-Cl bond. Thus, the selectivity of the reaction was dominated by two nitrogen bearing pyrimidine rings rather than by the halide group-bearing the pyrimidine ring.3. The N-arylation of halogenated fluorobenzenes with carbazole was selected as the model reaction. After optimizing of reaction conditions, a method for highly site-selective C-N bond-formation of halogenated fluorobenzenes with carbazoles is described. The selectivity of iodine and fluorine atoms on the aromatic ring of fluorinated iodobenzenes was initially determined in the copper-diisopropylethylamine catalytic system. By changing the position of the iodine atom on an aromatic ring from the 3- or 4-position to the 2-position, the preferred coupling site was switched from the iodine atom to the fluorine atom. Steric hindrance of fluorinated iodobenzenes is responsible for the selectivity switch. The metal-free system was able to handle a wide range of halogenated groups. Thus, a wide range of chlorinated, brominated, and iodinated N-arylated carbazoles were generated, which are widely useful in organic chemistry.4. A simple, practical and efficient superbase system for the direct alkynylation of trifluoromethyl ketones was developed without any additional ligand. Firstly, the direct alkynylation of 2,2,2-trifluoroacetophenone with phenylacetylene was selected as a model reaction to optimise the reaction conditions, in which a range of solvent, temperature, base, copper source and atmosphere were investigated. A wide range of functional groups on alkynes are compatible with the reaction conditions, including aryl acetylene, alicyclic, and aliphatic alkynes. The experiment on phenylacetylene H-D exchange indicating that the oxidative addition of copper to alkyne is the rate-determining step and the superbase promoted the step of oxidative addition of copper to alkyne to generate an active copper-alkyne complex which may increase the reaction rate. Finally, the resuts show that the reaction is practical and scalable, and could be scaled up to a gram scale without any problems.