Studies On Cycloaddition Reations Of N-vinyl-?,?-unsaturated Nitrones With Isocyanates And Activated Alkynes Reagents

Nitrones are the most efficient 1,3-dipoles used in cycloaddition reactions,participating in various cycloaddition reactions to further synthesize heterocyclic compounds,which are very important classes of synthons.Therefore,the application of nitrone is a very important topic in organic synthesis.In this thesis,we mainly studied the synthesis of nitrogen heterocyclic compounds by cycloaddition and rearrangement of N-vinyl-?,?-unsaturated nitrones with different electrophilic reagents.And based on the synthesized racemic nitrogen nine-membered heterocycles,kinetic resolution of the aza-heterocyclic was achieved by cooper combined with chiral ligand.This paper is divided into three parts:In the first part,under metal-free conditions,highly diastereoselective nine-membered heterocycles were prepared from the cycloaddition and rearrangement of N-vinyl-?,?-unsaturated ketonitrones and isocyanates.Notably,the prepared nine-membered heterocycles could produce 2,3-dihydropyrrolizines under heating conditions.Mechanistic studies showed that the nine-membered heterocycles might undergo decarboxylation,isomerization,aza-Michael addition,and aromatization to afford 2,3-dihydropyrrolizines in a one-pot reaction.In the second part,we developed the cycloaddition of N-vinyl-?,?-unsaturated nitrone and activated alkynes with catalyst of iron/copper to synthesize polysubstituted pyrrolizines in one pot.Besides,we explored the effects under various conditions such as diverse temperatures,solvents,bases,additives on the yields of pyolizines.And it was discovered that the N-vinyl-?,?-unsaturated nitrones had wide compatibility with activated alkynes with functional groups.The yields of polysubstituted pyrrolizine compounds were good.The discovery provided a basis for the further development andutilization of natural products and pharmaceuticals.In the third part,we explored the kinetic resolution of copper-catalyzed aza-heterocyclic compounds.According to the reaction mechanism proposed in the second part,the construction of the nitrogen nine-membered heterocycles from N-?,?-unsaturated nitrones and alkynes showed that,the racemic nitrogen nine-membered heterocyclic compounds can undergo the kinetic resolution under the copper and chiral ligands.Therefore,we studied the optimization conditions,such as solvents,temperature,ligands,and the scope of substrate.