| Polyaryl substituted（hetero）aromatic ring is the central structure of many drugs,bioactive molecules,agrochemicals,polymers and electronic materials.The pyridine ring of the polyaryl group is the basic scaffolds of many drugs and natural products,and plays an important role in organic synthesis and pharmaceutical chemistry.Palladium-catalyzed selective cross-coupling reaction is the most effective method for the construction of these compounds,However,the activity of the carbon halide bond（C-X）on the pyridine ring is similar,which leads to the defects of the traditional palladium catalytic system has some defects,such as harsh reaction conditions,poor selectivity,many side reactions and so on.How to improve the selectivity of the C-X bond has become the biggest challenge in the field of palladium-catalyzed cross-coupling reactions in recent years.The results show that the catalyst structure,especially the ligand structure,is the core factor to determine the selective reaction.At present,the ligands used are usually organic phosphine ligands,but most of the phosphine ligands are unstable in the air and seriously pollute the environment,which does not conform to the concept of green chemistry,which limits its large-scale application.Therefore,the development of non-phosphine ligands with stable air,low environmental pollution and high catalytic efficiency for selective reaction of（hetero）aromatic ring sites has become a research hotspot in the field of organic catalysis.In view of the above challenges,a series of N-heterocyclic carbene palladium complexes were designed and synthesized for palladium-catalyzed selective coupling reaction,and excellent selectivity was obtained.1.Three N-heterocyclic carbene palladium complexes were synthesized and characterized by 1H NMR and 13C NMR,compared with other nitrogen carbene palladium complexes with the same structure,the effects of electronic effect and steric hindrance effect on catalytic selectivity were investigated.The results show that the rigid large steric hindered nitrogen heterocyclic carbene ligands with diphenylmethyl in the ortho position of aromatic amines can protect the palladium center and hinder the rotation of pyridine ring after coordination with palladium,but the too high or too small steric resistance of nitrogen heterocyclic carbene will affect the catalytic activity and selectivity.The results show that K1,which is simple in synthesis and easy to obtain from raw materials and with large steric hindrance,can obtain highly selective monosubstituted coupling products of 2,5-dichloropyridine in high yield,and can continue to replace another chlorine atom on the pyridine ring by changing the base and solvent.The optimal reaction conditions were determined by condition screening,and then the substrate was extended to synthesize a series of monosubstituted and asymmetric substituted coupling products.2.By changing the structure of partial ortho substituents of N-aryl in palladium catalyst and replacing the rigid steric hindrance of diphenylmethyl with flexible steric hindrance,the selective conversion of2,5-dichloropyridine from mono-arylation to double substitution can be realized.The appropriate flexible variable steric hindrance isoheptyl of catalyst K7 meets the requirement of steric hindrance,and its variability enables the pyridine ring to rotate freely after coordination.Through the screening of the conditions,the optimum reaction conditions were determined,the substrate was studied,and a series of pyridine disubstituted coupling products were synthesized.By changing the framework structure of the catalyst,this paper achieves the effect of controlling the steric hindrance effect and electronic effect of the ligand,and emphasizes the importance of the design of the skeleton and N-aryl part in the design of the catalyst,which breaks the traditional concept of catalyst structure design,it provides a new method for site-selective arylation of polyhalogenated（hetero）aromatic rings and provides a new idea for other researchers in this field in the design and synthesis of metal-catalyzed ligands. |
