Study On The Reaction Of Constructing Spirooxindole N,O-heterocyclic Compounds Based On The Cycloaddition Of Nitrones

It is well known that spirooxindole compounds widely exist in indoline alkaloids,and they exhibit a wide range of biological activities.These spirooxindole compounds feature a quaternary carbon center at the C3-position and their synthesis is challenging owing to their inherent three dimensional geometry.Nitrone is a kind of widely used three-atom synthetic block.Its participation in cycloaddition reaction is an important method for the synthesis of heterocyclic compounds.It has a wide range of applications in organic synthesis,medicine and material science.My research is mainly the cycloaddition reaction based on N-vinyl isatin nitrones,providing green and new synthetic methods for natural active compounds and their analogues(with spirooxindole N,O-heterocyclic scaffolds).This paper is divided into two parts:In the first part,we developed the strategy of [3+2] cycloaddition of N-vinyl-2-isatin nitrones and arynes,and then selective rearrangement to synthesize spirooxindole-benzo[d]oxazoles and dihydrobenzofurans.We discussed the effects of temperature,base,solvent,and other conditions on the reaction.At the same time,we also explored the substrate scope of this reaction.The reaction had the advantages of short reaction time,mild reaction conditions,good functional group compatibility,simple operation,and easily available raw materials.This strategy provides a more efficient and convenient method for synthesizing spirooxindole-benzo[d]oxazole and dihydrobenzofuran compoundsIn the second part,we have developed a TFE-promoted [3+3] cycloaddition of N-vinyl-isatin nitrones with oxyallyl cations generated from α-tosyloxy ketones to prepare a variety of spirooxindole-1,2-oxazinan-5-ones derivatives with high diastereoselectivity.Mechanistic studies revealed that TFE played important roles not only as hydrogen-bonding to activate substrates but also reactive reagents to form an active N-alkyl-isatin nitrone intermediates.This strategy has mild reaction conditions,good yields,and a wide range of substrates.This strategy lays the foundation for studying the biological activity of these spirooxindole-1,2-oxazinan-5-one compounds.