Ttransition-metal Catalyzed Cyclization And Ring-opening Reaction To Construct Nitrogen-containing Heterocyclic Compounds

With the rapid development of society,the demand for drugs has also rapidly increased,but nitrogen heterocyclic compounds and their derivatives are widely used in pharmaceuticals and natural products,among which?-aminoketone derivatives,imidazole derivatives and isoquinolines.The use of ketone derivatives in pharmaceutical synthesis is also becoming more widespread.In this paper,the transition metal catalyzed cyclization of nitrogen-containing heterocyclic compounds to form?-aminoketones,imidazoles and isoquinolinone was investigated.This article includes the following three areas of work:The ring opening reaction of 2H-azirines and carboxylic acid catalyzed by Pd?OAc?₂was investigated.This reaction reports that 2H-azirines and a carboxylic acid undergo a C-N single bond cleavage and a thermal rearrangement reaction to construct an?-aminoketone derivative,and this method has the advantages of high atomic efficiency,excellent functional groupsuitability.UsingPd?OAc?₂asacatalystandchlorine[1,3-bis?2,6-diisopropylphenyl?imidazol-2-ylidene]silate as oxidant,using Li₂CO₃?lithium carbonate?and DMAP?4-Dimethylaminopyridine?as an additive,reacted in 1,4-dioxane for18 hours,and the optimum yield was 95%.The reaction is applicable to a variety of carboxylic acids?such as aromatic carboxylic acids,aliphatic carboxylic acids,even thiophene-2-carboxylic acids,furan-2-carboxylic acids and nicotinic acid are also suitable?and various azacyclopropanes.The palladium-catalyzed decarbonylation cyclization reaction between phthalimide and phenylene was investigated,which provided a new method for the synthesis of isoquinolinone derivatives.Under the protection of nitrogen,the reaction was carried out under the catalysis of Pd?PPh₃?₄,using cesium fluoride as the basic additive,and PhCl/tert-amyl alcohol?2:1?as the solvent,adding potassium t-butoxide to react at 120°C,with the yield up to 75%.This method is applicable to a variety of functional groups and can be used to prepare a series of isoquinolinone compounds.The results show that whether the substituent of phthalimide is electron withdrawing,neutral or push electron,the reaction can be carried out to obtain the corresponding product in 21-75%yield.The Pd?OAc?₂ catalyzed 2H-azirines participates in the[3+2]cycloaddition reaction to construct imidazole derivatives.The reaction was carried out by using ammonium hexafluorophosphate as an acid regulator,silver acetate as an oxidant,and DMAP as an additive,and reacting in 1,4-dioxane for 18 hours,and the yield was up to 88%.Some substrates have been expanded and the yields are moderate to good.