Palladium-catalyzed Heteroaryl C-H Arylation And The Synthesis Of Multiply Arylated Thiophenes

In recent years,the palladium-catalyzed direct arylation reaction has attracted widespread attention as a simple,highly efficient,environmentally friendly,atomic economic strategy for constructing?hetero?aryl compounds.At present,palladium-catalyzed direct arylation of C-H bonds has been made great progress.On the one hand,the Pd?OAc?₂/phosphine ligand catalytic system is the most effective catalytic system for catalyzing the direct arylation of C-H bonds,which is of great significance for the construction of bi?hetero?aryl skeleton structures.However,phosphine ligands have a variety of disadvantages such as tedious preparation process,instability under air,and large toxicity,which limits their large-scale application.On the other hand,phosphine-free palladium catalysts are widely used in the direct arylation of C-H bonds because of their simple preparation,low toxicity,relatively stable in air,and good catalytic activity.However,it still has the disadvantages of limited substrate range,high catalyst loadings?5%-10%?,and extremely low reactivity to heterocyclic compounds.Therefore,the development of a phosphine-free palladium catalyst system with excellent catalytic activity,air stability,and good adaptability to heterocyclic compounds has become a hot spot in the field of organic catalysis.In this paper,a?-diimine palladium complex?C1?with a flexible,large steric hindrance at the N-aryl moiety has been designed and synthesized,and its structure has been characterized by ¹H NMR,¹³C NMR,MS and X-ray single crystal diffraction.We examined the catalyst precursors via model reaction and the optimal conditions were established as:C1?0.1 mol%?,PivOH?30 mol%?,K₂CO₃?2 eq.?as the base,DMAc as the solvent,130°C for 12 h.The coupling of a series of heterocyclic?such as thiazole,furan,imidazopyridine,indolizine,isoxazole,imidazole,triazole,pyrazole,pyrene,pyrrole,and pyrazolidone etc.?with heterocyclic bromides which bearing various functional groups have been performed under the optimal reaction conditions,giving 92coupling products in good to high yields.The results showed that the phosphine-free catalyst system can conduct the coupling reactions of various heterocyclic compounds with heterocyclic bromides bearing different functional groups under lower catalyst loadings and air conditions,with the advantages of low catalyst dosage,wide substrate range,mild reaction conditions,and easy operation.Multiply arylated thiophenes have extensive application value in material chemistry and pharmaceutical chemistry due to its excellent photoelectric properties and biological activity.Simple and effective synthesis of multiply arylated thiophenes has become a research focus in the field of organic synthesis.This article attempts to use 3-thiophene boric acid as the starting material,and synthesize multiply arylated thiophenes with different aryl structures by combining Suzuki coupling reaction and C-H bond direct arylation reaction,developing a simple,practical and cost-effective route for synthesis of multiply arylated thiophenes...