Synthesis Of CF₃-Substituted Pyrazolidines And Pyrazolines

In recent years,N-acylhydrazones,as equivalents of imines,have drawn more and more attention in organic synthesis,due to they are more stable,easy to storage and easy to purify than imines.N-acylhydrazones have been widely used in medicine,pesticide,material and analysis reagents and other aspects.On the other hand,organofluorine compounds are also widely used in the fields of medicine,pesticides and materials.The incorporation of trifluoromethyl group into organic molecules can lead to great changes in their physicochemical and biological propeties,such as enhanced binding affinity,lipophilicity,metabolic stability,bioavailability and so on..Therefore,the introduction of trifluoromethyl groups into organic molecules and application of trifluoromethylated compounds in medicinal chemistry,agrochemicals and materials science are of great significance.Here,we tried to use stable and readily available trifluoromethylated N-acylhydrazones as trifluoromethyl building blocks to synthesize a series of CF3-substituted pryazolidines by [3+2] cycloaddition of trifluoromethylated N-acylhydrazones with alkenes.Hence,a simple and convenient method for introducing trifluoromethyl group into heterocyclic molecules is provided.The paper consists of three parts: The chapter one: [3+2] cycloaddition reaction of trifluoromethylated N-acylhydrazonesThis chapter mainly introduced [3+2] cycloaddition reaction of trifluoromethyated N-acylhydrazones as 1,3-dipole and various dipolarophiles catalyzed by copper salts,Lewis acids and organic catalysts,even without catalysts.The chapter two: [3+2] cycloaddition reaction of trifluoromethylated N-acylhydrazones with alkenesIn this chapter,a Lewis acid-catalyzed [3+2] cycloaddition of trifluoromethylated N-acylhydrazones with alkenes was explored,and a series of CF3-substituted pryazolidines were obtained in high yields.The reaction have following advantages: the use of cheap and readily available trifluoromethylated N-acylhydrazones as trifluoromethyl building blocks,mild reaction conditions and high reaction yield.Furthermore,the cycloadducts can be transformed into trifluoromethylated pyrazolines in excellent yields.The chapter three: [3+2] cycloaddition reaction of trifluoromethylated N-acylhydrazones with alkylidene oxindolesThe [3+2] cycloaddition reaction of trimethylallylated N-acylhydrazones and chiral alkylidene oxindoles was explored in this charpter.It was found that trifluoromethylated N-acylhydrazones could reacted with chiral alkylidene oxindoles catalyzed by Bu4 NI as phase transfer catalyst in the presence of potassium hydroxide,and the CF3-substituted 3-spirocyclic-2-oxindoles were obtained in good yields.