Study On The Construcion Of Arylated N-heterocyclic Derivatives Catalyzed By Bulky Sterically Hindered Carbene And ?-Diimine Palladium Complexes

Arylated N-heterocyclic derivatives are commonly found in the structures of natural products and drugs.The construction of arylated N-containing heterocycles is a hot topic in the field of organic synthesis.However,utilizing palladium-catalyzed C-H bond direct arylation and Suzuki-Miyaura reaction are important means for the efficient construction of arylated N-containing heterocycles.Most of these palladium catalysts are based on organic phosphines as ligands.These ligands are favored by people because of their excellent catalytic activity.However,because they are sensitive and easily deactivated in the air,and unfriendly to the environment,their application in industrial production has been greatly limited.The carbene and?-diimine palladium complex is a kind of phosphine-free palladium catalyst with high activity and simple preparation process.Therefore,to explore the regulations between structure and catalytic properties of carbene and?-diimine ligands,to screen palladium complexes that can effectively catalyze direct C-H bond arylation and Suzuki-Miyaura reaction,and to promote the study of C-H bonds direct arylation and the Suzuki-Miyaura reaction will be of great theoretical significance,which have a good application prospect for green chemical synthesis and low cost production of N-containing heterocyclic arylated compounds.In this paper,two kinds of bulky sterically hindered palladium complexes,namely carbene and?-diimine palladium complexes,were synthesized.Their catalytic conditions were screened and the catalytic activities were tested.102 N-containing heteroaryl derivatives were synthesized.1.Four acenaphthene-supported carbene palladium complexes C1-C4 with a diphenylmethyl substitution at the 4-position of N-aryl and a different alkyl substitutions at the 2,6-position were synthesized,and screening C4 as catalyst,51 five-membered N-containing heterocyclic arylated derivatives were synthesized by direct arylation.Screening C2 as catalyst,24 N-containing heterocyclic arylated derivatives were synthesized via the Suzuki-Miyaura reaction.C4 as catalyst,the optimal reaction condition for direct arylation reaction was obtained after screening,namely DMAc as solvent,K₂CO₃as base,PivOH as acid additive,0.05-0.5 mol%of C4,in air,at 130°C for 12 h.Subsequently,this catalytic system was applied to the C-H direct arylation reaction of a variety of five-membered N-containing heterocycles with different aryl bromides.51 five-membered N-containing arylated derivatives were constructed,and their yields were30 to 99%.C2 as catalyst,the optimal catalytic reaction system for the Suzuki-Miyaura reaction was obtained after screening,namely using K₂CO₃ as the base,anhydrous ethanol as the solvent,and C2 as the catalyst,0.5 mol%of palladium loading,in air,at 80°C for 4 h.The catalytic system was applied to the Suzuki-Miyaura reaction of different N-containing heterocyclic chlorides with different phenylboronic acids.24 N-containing heterocyclic arylated derivatives were constructed with yields 9 to 97%.2.The?-diimine palladium complex K1 supported by bulky ancenaphthyl backbone with large sterically hindered groups at the2,6-position of N-aryl moieties was synthesized.27 arylated derivatives of imidazo[1,2-a]pyridines were synthesized via direct arylation reaction catalyzed by K1.K1 was compared with PdCl₂ and?-diimine palladium complexes K2-K3,which confirmed the advantage of K1 as a catalyst.On this basis,the optimal conditions for direct arylation reaction was obtained after screening,namely DMF as the solvent,K₂CO₃ as the base,PivOH as the acid additive,0.3 mol%of K1,in air,and at 130°C for 12 h.Then the catalytic system is applied to C-H bond direct arylation reaction of1A-3C with four different aryl bromides.27 arylated derivatives of imidazo[1,2-a]pyridines at the C-3 position were constructed with yields43 to 99%.The C-H bond direct arylation and Suzuki-Miyaura reaction of N-containing heterocycles catalyzed by bulky sterically hindered carbene and?-diimine palladium complexes confirmed that the catalytic systems of C2,C4 and K1 have the characteristics of mild catalytic conditions,high catalytic yield,wide applicability of substrates,high catalytic activity and good regioselectivity.They can be carried out under water-containing aerobic conditions without strict restrictions on anhydrous and inert atmospheres,and could construct arylated derivatives of N-containing heterocycles,which would have important theoretical significance and potential industrial application value for the synthesis of N-containing bioactive compounds and functional materials.