Organocatalytic Synthesis Of Isoxazole, Oxazoline And Pyrazole Compounds Through 1,3-dipolar Cycloaddition

The 1,3-dipolar cycloaddition is a classical reaction for the synthesis of five-membered heterocyclic compounds in chemical reactions,also known as Huisgen reaction.The reaction refers to the process in which the 1,3-dipole reacts with the alkenes,alkynes and their derivatives to form five-membered heterocyclic compounds.1,3-Dipole is generally divided into propylene dipole and ethinyl or propylene dipole,such as azomethine ylide,azomethine imine,nitrile oxide,nitrile imine and so on.Conditionally,the 1,3-dipolar cycloaddition is easy to be carried out and the reaction conditions are mild,because of its character which is less affected by the solvent dielectric constant and polarity.The reaction has been widely used in the synthesis of heterocyclic compounds.This thesis is mainly composed of three parts: 1.Organocatalytic 1,3-dipolar cycloaddition of nitrile oxides to allenoatesIsoxazoles is one of the most significant examples five-component heterocyclic compounds,as a result isoxazoles become the focus of a lot of chemists.The most convenient way to obtain isoxazoles might be the addition between acetylenes and nitrile oxides.This paper described a way of constructioning the isoxazoles through the 1,3-dipolar cycloaddition between oxime halides and allenoates.In the presence of DABCO and Et3 N,the reaction could generate various isoxazoles with 55-90% yields in a mild condition.After that,both gram reaction and the large variety of the substituent products have high yields,barely impacted by electron effect and steric effect.Considering the large variety of the starting materials,we believe that this work will have a wide use in the future.2.Organocatalytic double 1,3-dipolar cycloaddition of nitrile oxides to allenoatesBoth isoxazoline and spiroisoxazoline scaffolds are featured in a series of natural products and synthetic products with extensive biological activities,and they are also significant synthetic intermediates in organic synthesis.The synthesis strategy of most spirocyclic structures is to construct a new ring on the existing carbon ring or heterocyclic ring.Very limited reports on the construction of two rings via a double 1,3-dipolar cycloaddition for a spirocyclic compound have been reported.Therefore,we have developed a synthesis strategy of constructing the spirobiisoxazoline skeleton through the double 1,3-dipolar cycloaddition between oxime halides and allenoates.In the presence of DABCO and Et3 N,a series of spiroisoxazoline compounds are synthesized by one-pot in 55-90% yields through a double [3+2] cycloaddition between oxime halides and 2-substituted buta-2,3-dienoates.Meanwhile,the reaction conditions are mild and the substrate is suitable for the reaction.The cycloaddition is also immune to steric effect and electron effect.We also carried out derivative reaction and detailed mechanism verification.In conclusion,the reaction provides a straight-forward pathway for synthesis of spiro compounds in a mild reaction conditions.3.Organocatalytic 1,3-dipolar cycloaddition reaction between ?-functionalized ketones with nitril iminesPyrazoles are significant examples of five-membered heterocycles,which were found in a variety of known compounds and natural products,most of them have a wide range of pharmaceutical and agricultural chemical activity,Pyrazoline,as the derivatives of pyrazole,are important intermediates in medicine and dyes.Therefore,pyrazoles have broad research and development prospects.In this paper we choose organic small molecule as catalysis of the reaction with lower toxicity to synthesize the target product.In the presence of Et3 N,we choose DMAP which is cheaper and lower posion as catalyst.A series of polysubstituted pyrazole compounds are synthesized in 67-98% yields via a 1,3-dipolar cycloaddition between nitrile imines and ?-functionalized ketones.At the same time,we use less catalyst and the chemical reaction is economical.The 1,3-dipolar cycloaddition could generate various pyrazoles in high yields and regioselectivities with nitrile imines and 1,3-dicarbonyl compounds,affording a new synthesis strategy of constructioning the pyrazoles.