1,3-Dipolar Cycloaddition Reaction Based On 2-amino-1-indanone

As one of the research hotspots in the field of organic synthesis,the 1,3-dipolar cycloaddition reaction has developed rapidly in recent years.The 1,3-dipolar cycloaddition reaction is characterized by high efficiency,high atom economy,mild reaction conditions and so on.So it can provide a simple and effective green synthesis method for the construction of cyclic compounds.Among them,as a common 1,3-dipole,the 1,3-dipolar cycloaddition reaction involving azomethine ylide has a prominent position in the construction of a five-membered nitrogen-containing heterocyclic ring.Indanone is a very important structural motif and is widely present in a variety of natural products and pharmaceutically active molecules.At the same time,as an important oxygen-containing heterocyclic structure,the chroman skeleton also has a wide range of biological and pharmaceutical activities.Therefore,the development of synthetic methods to assemble indanone and chroman skeletons has great practical significance.However,up to now,although the biological activities of indanones have been extensively studied,few reports have been reported on cycloaddition based on indanones.On the basis of the previous work of our group,in this paper,it is hoped that 2-amino-1-indanone can be used as a novel precursor of azomethine ylide to participate in the intramolecular 1,3-dipolar cycloaddition reaction to synthesize some complex spiro indanone-chroman compounds.The specific work of this paper is as follows:The intramolecular 1,3-dipolar cycloaddition reaction of azomethine ylide in situ formed from 2-amino-indanone and benzaldehyde ester derivatives was directly carried out under the catalysis of diphenyl phosphate.By screening the reaction parameters such as catalyst,solvent and catalyst loading,the optimal reaction conditions were determined.Then,the reaction is capable of obtaining a series of spiro indanone-chroman compounds in excellent yield(35-99 %)and diastereoselectivity(>20:1 dr).Finally,when we run the reaction under chiral phosphoric acid catalysis,a preliminary 20% ee could be obtained,indicating viability of an asymmetric version of this reaction.