Studies On Nickel-catalyzed Novel Reactions Of Isocyanides And Thioureas

Thiazole derivatives are an important heterocyclic compounds,which possess good biological and pharmacological activities because of their unique chemical structure.As valuable C1 building blocks,isocyanides play an important role in synthesis of the nitrogen-containing heterocycles.Tremendous advances was made in nickel-catalysis over the past half-centry,several key properties of nickel,such as ready access to multiple oxidation states,facile oxidative addition,good stability and low costs,allowed the development of a broad range of innovative reactions.In chapter Ⅰ,we summarized the traditional methods in synthsis of thiazole derivatives,isocyanide insertion reactions and the recent advances of nickel catalysis.In chapter Ⅱ,a facile,efficient and eco-friendly strategy for synthesis of triiminothiazole derivatives was developed by nickel-catalyzed isocyanide insertion with thioureas.In this transformation,isocyanide serves as an efficient C1 connector,which further inserted into two simple nucleophiles(S-H/N-H).The optimization of reaction conditions are as follows: 1 equiv of 1,3-diphenylthiourea,2.5 equiv of isocyanocyclohexane,3 mol % Ni(acac)2 as the catalyst,acetone as the solvent at 50 oC for 1h.Different kinds of triiminothiazole derivatives could be synthesized in good yields.Then,the reaction mechanism was proposed based on a series of control experiments.To demonstrate the potential of the current method for practical synthesis,a preliminary study on gram scale reaction was carried out,and 85% yield triiminothiazole was obtained.Structures of all the triiminothiazoles was confirmed by IR,1H NMR,13 C NMR,HRMS.The most significant specialty of the reaction is low cost and low loading catalyst,high atomic economy,broad substrate scope,green solvent,simple operation and efficent gram scale reaction.