The Hydration And Cyclization Of Copper-involved Propargylamine With Hypervalent Iodine Reagents

The combination of copper and hypervalent iodine reagents is an important tool in organic synthesis,mainly used for the synthesis of drug molecules,natural products and chemical materials.This thesis includes three parts of the research work.In the first part,the copper-mediated hydration reaction of alkynes with hypervalent iodine reagent1-chloro-1,2-phenyliodooxyol-3-(1H)-one was developed to synthesize α-halogen ketone compounds in one step.In the second part,the copper-catalyzed cyclization of N-(prop-2-yn-1-yl)amides with 1-chloro-1,2-phenyliodooxyol-3-(1H)-one as the oxidant to form oxazole derivatives.In the third part,an efficient method for the synthesis of dihydropyrimidin-4-ones from N-acetyl-1-phenylpropargylamine and sulfonyl azides via copper-catalyzed click reaction.The following is the main content of this work.(1)The copper-mediated hydration reaction of hypervalent iodine reagent with alkyneIn this part,propargylamine compounds were used as raw materials.α-Chloroketone derivatives were synthesized with high regioselectivity through the copper-mediated hydration reaction of alkynes with hypervalent iodine reagents.The oxidant1-chloro-1,2-phenyliodooxyol-3-(1H)-one plays a crucial role in the synthesis of versatile chloromethyl ketones from terminal alkynes.Then,we explored the reaction scope of the substrates and successfully obtained a set of α-chloroketone in good yields.This method has the advantages of cheap metals,short reaction time and easily obtained raw materials.(2)Copper-catalyzed cyclization of N-(prop-2-yn-1-yl)amides with hypervalent iodine reagentsThe oxazole skeleton is prevalent in many natural products and biologically active molecules.There is no report on copper-catalyzed cyclization of alkynes with hypervalent iodine reagents to synthesize oxazole compounds.The oxazole derivatives were synthesized by Cu(I)-catalyzed intramolecular cyclization of propargyl amide with hypervalent iodine reagent,using a readily available N-(prop-2-yn-1-yl)amides substrate as raw materials.This section was discovered by chance in the first section of expanding the substrate scope.This method has the advantages of cheap metals,short reaction time and easily obtained raw materials.(3)Copper-catalyzed synthesis of dihydropyrimidinones from propargyl amides and p-toluenesulfonyl azideThe molecules with dihydropyrimidinone skeletons are widely used in the area of pesticides,medicines and materials chemistry.We have developed an efficient method for the preparation of dihydropyrimidin-4-ones from N-acetyl-1-phenylpropargylamine and sulfonyl azides via copper-catalyzed click reaction.This method has some advantages,such as mild reaction conditions,high yields of products,good functional group tolerance.