N-heterocyclic Carbene Palladium Complexes:Applications For The Synthesis Of Active Ingredients Of Traditional Chinese Medicine Including Arylamine And Biphenyl Unit

The unit of arylamines and biphenyl are important for active ingredients of Traditional Chinese Medicine and natural products.Transition metal Palladium-catalyzed Buchwald-Harting amination reaction has emerged as one of the most valuable synthetic approaches for the construction of C(sp2)-N bonds and the Suzuki-Miyaura coupling reaction which are now recognized as highly versatile tools for C-C bond formation.These methodologies are widely used in the research of Active Ingredients of Traditional Chinese Medicine Including Arylamine and Biphenyl Unit.In recent years,N-heterocyclic carbene palladium complexes as a efficient catalyst which has the advantages of easy preparation,species diversity in the water,air stable,non-toxic,environmentally friendly,and can regulate the steric and electronic by changing the substituents on the nitrogen atom,were widely used in the Buchwald-Harting coupling reaction and Suzuki-Miyaura coupling reaction.ObjectiveTo synthesize a series of compounds containing unit of arylamines by Buchwald-Hartwig coupling reaction and and compounds containing unit of biphenyl by Suzuki-Miyaura coupling reaction.These researchs aimed to provide new methods and ideas for the synthesis,semi synthesis and structural modification of Active Ingredients of Traditional Chinese Medicine or natural active products and their derivatives containing unit of arylamines and biphenyl.MethodsA series of N-heterocyclic carbine palladium complexes with different electronic effects and steric hindrance were designed and synthesized based on the large number of literatures.The synthesized N-heterocyclic carbene palladium complex was used as catalyst;(1)the aryl chlorides and amines as the reaction substrate of Buchwald-Harting coupling reactions.(2)aryl chlorides and aryl boronic acids as substrates the reaction substrate for Suzuki-Miyaura coupling reactions.The catalytic reaction was carried out under the air condition,and the factors affecting the reaction such as the catalysts,loading of catalyst,reaction solvents,bases and temperature were investigated by orthogonal design experiment.Finially,the optimized reaction conditions were determined.Under the optimized reaction conditions,a series of aromatic amine compounds and biphenyl compounds were synthesized,and the target product was separated and purified.The structure was verified by 1H NMR,13 C NMR and MS.1.The Buchwald-Hartwig coupling reaction of aryl chlorides with amines2.Suzuki-Miyaura coupling reaction of aryl chlorides with arylboronic acids Results1.N-heterocyclic carbine palladium complex C1-C6 which has different electronic effects and steric were sytheneized and characterized.The crystal structure of single crystal was obtained by the single crystal diffraction.C1-C6 as a catalyst,the optimized conditions of aryl chlorides with amines in Buchwald-Hartwig coupling reactions was screened;with N-heterocyclic carbene palladium complexes C3(0.1 mmol%)as catalyst,1,4-dioxane as solvents(3ml),KOtAm(1.5 mmol),aryl chlorides(1 mmol),amines(1.2 mmol),reaction for 2 h in the air at 100.30 arylamines were obtained and characterized.2,N-heterocyclic carbine palladium complex C7-C8 which has large steric on skeleton were sytheneized and characterized.C7 and C8 were tested by single crystal diffraction,and the corresponding single crystal structure was obtained.C7 and C8 as catalyst,the optimized conditions of aryl chlorides with arylboronic acids in Suzuki-Miyaura coupling reaction was screened;N-heterocyclic palladium complexes C7(0.05 mmol%)as catalyst,ethanol as solvents(3ml),K3PO4 as the base(1.5 mmol),aryl chlorides(1 mmol),arylboronic acids(1.2 mmol),reaction for 4 h in the air at 80.32 biphenyl compounds were obtained and characterized.ConclusionIn this paper,the designed and obanied N-heterocyclic carbine palladium complexes which have the advantages of stable air,simple synthesis,high catalytic activity,mild catalytic conditions,easy operation can be used to efficiently catalyze the Buchwald-Hartwig coupling reaction of aryl chlorides with amines and the Suzuki-Miyaura coupling reaction of aryl chlorides with aryl boronic acids in air.This study has a certain reference value for the synthetic,semi synthetic or structural modification research of active ingredients of Traditional Chinese Medicine which containing unit of arylamines or biphenyl.