Pd-Catalyzed Intramolecular Thiophene C-H Addition To Nitriles:Synthesis Of Thiophene-Annulation

The reaction of transition-metal-catalyzed aromatic ring hydrocarbon bonds with carbon-carbon and carbon-Heteropoly bonds is a simple and effective method to construct annulation compounds.Among them,transition-metal-catalyzed reactions of aromatic rings and aromatic heterocyclic C-H addition to nitriles have attracted much attention and developed rapidly.However,the method of transition-metal-catalyzed the synthesis of thiophene-annulation by cyanic addition has not been reported.Thiophene derivatives containing thiophene sacaffolds,4,5,6,7-tetrahydrobenzo[b]thiophene,benzo[b]thiophene,are widely applied in biological,pharmaceutical and material fields.Therefore,the synthesis of thiophene-annulation compounds is of great significance.We designed a transition-metal-catalyzed C-H activation tadem cyclization reaction of thiophene to synthesize thiophene derivatives.The following is the main research content of this paper:(1)We have developed a method of atomic economy: the synthesis of 4,5,6,7-tetrahydrothiophene derivatives via C-H addition of thiophene bearing cyanohydrin units at the C(3)positions to cyano-group catalyzed by transition metal palladium.First,different solvents,catalysts and ligands were screened,and the best reaction conditions were established.Then,the universality of substrates was investigated,which proved that this method is widely applied.On this basis,we have synthesized fused pyrrole and furan analogues.Finally,we have studied the reaction mechanism,the further transformation and application of the target products.(2)We designed a strategy for the synthesis of aminobenzo[b]thiophene derivatives via Pd-catalyzed C-H addition of 3 substituted thiophene containing cyanohydrin units.The maximum yield of the target product is achieved by screening the reaction conditions and the predesign of the substrate.Our research is still continuing,and there are still some challenges.We will continue to optimize the reaction conditions,and we hope to be able to produce target products with high yield.