Palladium-catclyzed Direct C-H Arylation Of Pyridine N-oxides Wieh Potassium Aryl- And Heteroaryltrifluoroborates

2-aryl pyridine structure units are important structure group of heterocyclic aromatic compounds. They have found widespread exist in many pharmacophore, natural products, functional materials and the ligands. Its corresponding derivatives are also valuable synthetic building blocks. Due to the effectiveness of the chemical and the importance of biological, the synthesis and application of 2-aryl pyridine compounds got a lot of attention. However, there remains a significant challenge for the direct functionalization of the pyridine ring due to its low reactivity and poor regioselectivity. On the one hand, electrophilic aromatic substitution usually takes place with great difficulty. On the other hand, pyridine derivatives are usually unreactive toward aromatic nucleophilic substitution without a good leaving group. Additionally, what severely limits their application in cross-coupling reactions is the inherent instability and difficulties during the synthesis of 2-pyridyl organometallics. So it encouraged organic chemists to explore the direct functionalization of N-activated pyridinium species, such as pyride-N-Oxides specie, which are very important intermediates for the C-H bond activation and functionalization of the pyridine ring in synthetic organic chemistry as well as in the chemical industry. Recently, numerous efforts have been devoted to the development of efficient approaches for the arylation of N-oxides. At the same time, palladium catalysts have been proved quite effective catalyst for catalytic functionalization. Therefore, the synthesis of direct functionalization of 2-aryl pyridine-N-oxide research has important theoretical significance and practical significance.The work of this paper is mainly divided into the following three parts:（1） By selecting the reaction of pyridine-N-oxide with Potassium phenyltrifluoroborate as the model reaction to find the optimized conditions.Several reaction parameters such as the kind and amount of the solvents, kind and amount of catalysts, oxidant species and dosage, the dosage of additives and species as well as the ratio of substrates was investigated respectively. Finally the optimal conditions were established as the following: the standard substrate Potassium phenyltrifluoroborate in an amount of 0.15 mmol, pyridine-N-oxide in an amount of 0.53 mmol, Pd（OAc）₂ 10 mol %, Ag2 O 2.0 equiv., the additive TBAI 20 mol %, 1, 4-dioxane（0.5 mL） as solvent, at 90 oC for 17 h in a sealed tube and under the condition the yield was 95%.（2） We next set out to explore the scope and limitation of the reaction under the optimum reaction conditions and further modification reaction. We studied different substituents of Potassium phenyltrifluoroborate and different substituents of pyridine-N-oxide. The results show that the optimal reaction condition has a good adaptability.（3） According to the related literatures, we proposed the possible mechanism of the reaction. It is verified through a series of experiments to explore the reaction mechanism.In conclusion, we successfully realized palladium-catalyzed the C-H bond activation and functionalization of pyridine-N-oxide, obtained a series of 2-aryl pyridine-N-oxide compounds in high productivity and almost no by-products.