8-Aminoquinoline-Directed Copper-Catalyzed One-Pot Synthesis Of 1,3-Enynes

1,3-Enynes are valuable synthons in the field of organic chemistry and can be used for the synthesis of natural products,pharmaceuticals,and functional materials.Numerous synthetic methods have been developed to synthesize of 1,3-enynes.Among these methods,the dimerization of alkynes has attracted considerable attention due to its perfect atomic economy.For further enhance the practicability of this method,we developed a copper-catalyzed one-pot synthesis 1,3-enynes from terminal alkynes,with high chemo-,regio-,and stereoselectivities,in addition,and the possible mechanism would be discussed.In this reaction,2-chloro-N-（quinolin-8-yl）acetamide（1a）and phenylacetylene（2a）were selected as model substrates and then,the catalyst,ligand,solvent,base,time and temperature were investigated.Finally,the reaction was conducted in the presence of CuI（10 mol%）,1,10-phenanthroline（20 mol%）,and Cs₂CO₃（1.2 equiv.）in DCM at room temperature or 35°C for 48 h.Under the optimized conditions,the conjugated 1,3-enynes could be obtained in69?95%yields（using single terminal alkyne）or 53?89%yields（using two different terminal alkynes）.The wide availability of the simple terminal alkynes,cost effectivity of Cu catalyst,mild reaction conditions,good functional group tolerance,and experimental simplicity rendered the current method highly useful for the synthesis of（E）-1,3-enynes.Mechanistic studies indicated that 8-aminoquinoline played a key role in this reaction as a directing group,and allene was the active intermediate of the reaction.gram-scale synthesis and product derivatization proved the good practicability of this reaction.The products were characterized by ¹H NMR,¹³C NMR,high-mass and IR.