Asymmetric Synthesis Of Dihydroisoquinoline And Triazine From ?-diazo Compounds

Heterocyclic compounds not only exist in natural products,drug molecules,and agrochemicals,but also serve as ligands of transition metal complexes.Moreover,it is widely used in material science and organic synthesis.For example,1,2-dihydroisoquinolines have various potential biological activities,and have inhibitory effects on tumor cells,viruses,and fungi;1,2,4-triazine and its derivatives have multiple biological activities,such as anti-virus,protein kinase C? inhibitor and anti-tumor activity.Therefore,it is of great significance to develop efficient and novel methods to synthesize such heterocyclic compounds.a-Diazo compounds,as an important synthon,are widely used in asymmetric synthesis.The diazo compounds can be used as a 1,3-dipoles,in which the ?-carbon is nuchleophilic and the terminal nitrogen is electophilic.The asymmetric reactions involving diazo compounds mainly fall into the following categories:firstly,under the catalysis of transition metal catalyst,the diazo compound releases a molecule of nitrogen to generate carbene intermediates,and then X-H(X=C,N,O,S,Si,etc.)insertion reaction,cyclopropanation reaction and rearrangement reaction;secondly,react at its nucleophilic ?-carbon to construct multifunctional diazo compounds;thirdly,the electrophilicity of the terminal nitrogen of the diazo group is used to carry out an asymmetric reaction to construct hydrazone.Finally,under the action of a chiral catalyst,the 1,3-dipolar cycloaddition reaction is catalyzed to construct heterocycles.Based on the importance of heterocyclic compounds and the nature of diazo compounds,this thesis will demonstrate the application of ?-diazo compounds to construct three types of heterocyclic compounds:Part ?:Developed a method to construct 1,2-dihydroisoquinoline ?-aminophosphonate or carboxylate compounds containing C1 chiral center via dearomatization of isoquinoline.That is,by designing and synthesizing chiral phosphoric acid catalysts to catalyze the asymmetric dearomatization reaction of isoquinoline,?-diazophosphonate or carboxylate and pyrocarbonate.The product can be further transformed into ?-amino phosphonate or carboxylate.Part ?:By designing and synthesising a novel phase transfer catalyst derived from cinchona,the first example of asymmetric(3+3)cycloaddition of diazophosphonate/diazosulfone and azomethine ylide was successfully achieved with high enantioselectivity.A method for obtaining optically pure isoquinolinotriazine with high enantioselectivity and high yield was established.The obtained product can be transformed into multi-substituted tetrahydroisoquinolinohexahydrotriazine with three chiral centers.On the other hand,the catalytic product can also be transformed into a phosphoramidate containing a chiral quaternary carbon center.Part ?:Design and synthesis of quinine-derived phase transfer catalysts,and used in catalytic asymmetric(3+3)cycloaddition reaction of ?-diazophosphonates with imidates to construct multifunctional chiral phosphonotriazines.