Palladium-Catalyzed Aminomethylation And Cyclization Of Enynol To O-Heterocycle Confined 1,3-Dienes

O-heterocycle confined 1,3-diene compounds are an important class of structural molecules,which are widely prevalent in biologically active natural compounds and pharmaceuticals.Therefore,it is of great significance to develop a new and effective synthetic strategy for the construction of O-heterocycle confined 1,3-diene compounds.Our research group has been committed to the research strategy of C-N bond activation and has developed unique aminal chemistry.Based on the unique reaction properties of the cyclopalladium complex,two new catalytic reaction modes were established that nucleophilic attack of the palladium center and nucleophilic attack of the carbon center.According to the previous reports,we hope to utilize simple enynol and aminal to construct O-heterocycle confined 1,3-diene compounds.However,the reaction mode may still suffer from the competition of other intermolecular nucleophiles such as the aminal or the amine due to comparatively weak nucleophilicity of the alcohol.On this basis,a simple and effective synthetic strategy for the synthesis of oxygen heterocyclic 1,3-diene compounds has been established by the intramolecular aminomethylation and cyclization reaction of enynol,applying the substrate control,the electrophilicity of cationic allylpalladium as well as oxidative addition of allylamine to Pd(0).Using raw materials hex-6-en-4-yn-1-ol and aminal as standard substrates,through systematic screening of conditions,the optimal reaction conditions were determined:5 mol%cationic palladium Pd(Xantphos)(CH3CN)2(OTf)2 as the catalyst,DME as the solvent under the reaction temperature of 100℃ for 12 hours.Under the optimized conditions,we systematically studied the reaction performance enynols and aminals(32 substrates in total),which exhibited good reactivity and functional group compatibility.The 1,3-diene compound with 5,6,8-membered oxygen heterocyclic ring was obtained with the highest yield of 96%.At the same time,gram-scale experiments could be smoothly conducted on a 10 mmol scale,delivering the corresponding product in excellent yield.The product could be converted to the unsaturated aldehyde and alkenyl iodide by further functional group transformation.The mechanism of the catalytic reaction was studied in detail through the control experiments,and a reasonable reaction path was proposed,which provided a new catalytic strategy for the synthesis of O-heterocycle confined 1,3-diene compounds.