Construction Of Nitrone And Its Application In The Synthesis Of Nitrogen Heterocycles

Nitrone,served as an important 1,3-dipole in organic synthesis,can participate in many chemical reactions to build a wide variety of nitrogen heterocyclic compounds.Therefore,the synthesis of nitrone in organic chemistry is a very important topic.This thesis mainly focused on the synthesis of N-aryl ketonitrones.The scope and mechanism of the reaction were also discussed.Spirofluorenylpiperidin-4-ones were further prepared by cycloaddition of fluorenone N-aryl nitrones with methylenecyclopropanes and sequential 1,3-rearrangement.This thesis could be divided into the following three parts:In the first part,we developed a metal-free N-arylation of ?,?-unsaturated N-aryl ketonitrones compounds by the reaction of oximes and diaryliodonium salts.The effects of different solvents,bases and reaction time were screened.DFT calculations suggest that N-arylation products are formed by[1,3]-phenyl migration of an O-coordinated oximate complex via a four-centered transition state,while the O-arylation products are formed by[1,3]-phenyl migration of a N-coordinated oximate complex.In the second part,we investigated the method for the synthesis of(Z)-N-aryl oxindole nitrones compounds by selective N-arylation of oximes bearing multiple nucleophilic sites.The effect of different solvents and bases were studied.Through the study of different substrates,it was found that the substrates scope was broad and the yield was excellent.Studies on the oxime structures revealed that the pyrroline ring and carbonyl group in 3-(hydroxyimino)indolin-2-ones played important roles in the selective N-arylation process.The N-aryl oxindole nitrones could be prepared rapidly and easily at the gram scale.In the third part,we studied the synthesis of spirofluorenylpiperidin-4-ones by cycloaddition of 9-fluorenone N-aryl nitrones with methylenecyclopropanes and sequential 1,3-rearrangement.The effects of different solvents and temperature on cycloaddition and 1,3-rearrangement were screened.When chiral methylene cyclopropane is involved in the reaction,we find that the stereochemistry of spirofluorenylpiperidin-4-ones could be controlled by the cycloaddition strategy.And the spirofluorenylpiperidin-4-ones could also be obtained from nitrone in high yield in one-pot reaction.