Tandam Cyclization Reactions Triggered By Allyl Substitution For The Construction Of Nitrogen-Containing Heterocycles

Nitrogen containing heterocyclic compounds is a kind of important organic compounds,which not only exist widely in nature but also relate to human health,life science,material science and other sciences.Hence,the efficient construction of heterocyclic compounds is hot research area of modem organic synthetic chemistry,and promotes the development of organic synthetic chemistry.How to realize the structural diversity of heterocyclic molecules to lay the material foundation for their functionalization while improving their synthesis efficiency and selectivity is an important topic in this research field.In this dissertation,the latest typical research advances in this field were expounded,and asymmetric synthesis of heterocyclic compounds triggered by allylation reaction were investigated based on three aspects:Lewis acid activation,tamdem cyclization and inverse-electron-demand palladium-catalyzed asymmetric cycloaddition reactions.In the first part of the work,the[3+2]cycloaddition reaction between vinylazocyclopropane and indoles was realized without the participation of transition metals by using the activation strategy of Lewis acid.Under the standard condition(Et3B as an activating reagents,tBuOK as a base),a series of pyrroleindoline were build in 38-96%yield and 2:1 to 7:1 dr.At the same time,more complex multi-ring structures can be constructed through simple functional group transformation.In addition,the strategy can be further extended to the[3+2]cycloaddition reaction of vinyloxirane with indoles,in which the tetrahydrofuranindolines were constructed in one step with 82-96%yield and 3:1 to 9:1 dr.In the second part,the asymmetric allylation/intermolecular cyclization of vinylbenzooxazinone and amine was realized by using the co-catalytic cyclization strategy and a series of chiral indoles and quinazolines were generated.In this study,we used vinyl benzooxazinone as the allylation precursor,and realized palladium-catalyzed branched selective asymmetric allyl amination via hydrogen bonding direction between nitrogen anion and nucleophile alkyl amine in 1,4-dipole intermediate stabilized by palladium,and constructed a series of 2-amino substituted allyl amines in 64->99%yield and 85-99%ee.With the help of a reasonable combination of palladium-catalyzed allylation and palladium-catalyzed double bond haloamination/photocatalytic oxidation cyclization,after the guiding work of the N-group,it is directly used as a nitrogen source in the next tandam cyclization reaction.Under the mild conditions,the construction of multi-substituted chiral indoline and chiral quinazoline in one pot with high efficiency and high stereoselectivity was realized(62-98%yield,94-98%ee,>95:5 dr).In the third part,we tried to control both the branched selectivity in palladium-catalyzed allylation and the nucleophilic site of 5-methyl-2(3H)-furanone by hydrogen bond direction and optimization of chiral sulfur-containing phosphine ligands which were developed by our group,so as to realize the[4+2]cycloaddition reaction between vinyl benzoxazinone and 5-methyl-2(3H)-furanone derivatives.Generally chiral multisubstituted tetrahydroquinolinones were built in with high yield,high stereoselectivity(54-99%yield,73-94%ee,up to>95:5 dr).At the same time,the reaction mechanism and stereoselectivity were explained by using DFT theory calculation method in cooperation with professor Yu Lan.It is worth mentioning that the strategy was successfully extended to the asymmetric cycloaddition reaction of ethylbenzooxazinone with azlactone and derivatives.