Asymmetric Three-component Aminomethylation Of Trapping Diazo Derived Intermediates With 1,3,5-Triazines

Amino compounds widely exists in the nature.Due to its various biological and pharmaceutical activities,the researches to construct amino compounds had become an important part of organic synthesis methodology learning.Mannich reaction,which uses imine subustrate as nitrogen containing building block,form the new C-C bond and construct the new amino compounds through nucleophilic addition of imine.Further,it could introduce chiral ligand and chiral organo-catalyst into the reaction system to control the stero-selectivity.Surrounding the Mannich reaction,it has been built up a series of mature and detailed works to promote the Mannich reaction into a general protocol for amino compounds construction.Multi-components reactions(MCRs),as its high efficiency in building structure diversity and step economic,have been proved a powerful tool for complex structure formation.And aminomethylation,for the istablity of formaldehyde derived imine or iminium which can only be in-situ generated,has remained as a challenging field in the Mannich reaction researches and deliveried a limited amount of records.Among these years,our group developed a series of Rh(II)\chiral phosphoric acid cooperative catalyzing aryl aldehyde derived imine to trap active ylide and zwitterion intermediates to form asymmetric Mannich-type trapping multi-components reactions.This dissertation mainly introduces the 1,3,5-triaryl-1,3,5-triazines,as a Mannich reagent precursor,could in-situ detrimerized into unstable formaldimine monoer,then involve our previous developed strategy of Rh(II)/chiral phosphoric acid cooperative catalysis to trap the diazo derived active intermediates via the dual hydrogen bonding activation mode from chiral phosphoric acid to form a variety of amino group contained skeleton.Compared to previous aminomethylation reports based on the nucleophile activation mode directed by primary amine or secondary amine catalyst and with the narrow nucleophile substrate scope of ketones or 1,3-dicarbonyl compounds which both perform generally similar carbonyl ?-position aminomethylation,our electrophile activation mode based aminomethylation indeedly conduct a novel and efficient complement to the aminomethylation catalysis strategy while overcoming the substrate limitation among the nucleophile activation mode.This stategy provides a new avenue for development of new aminomethylation reactions.In chapter 2,it reports an enantioselective Rh(II)/chiral phosphoric acid cocatalyzed trapping of alcohol and diazo ketone derived oxonium intermediate with 1,3,5-triazine as electrophilic aminomethylation reagent to afford chiral ?-hydroxyl-?-amino ketone structure which has appeared in some reports with promising pharmarceutical activities.It's the first chiral phosphoric acid dual hydrogen bonding activation mode based oxonium ylide trapped asymmetric multi-components aminomethylation reaction.The transformation has a wide substrate scope of aryl alcohol,simple aliphatic alcohol and even complex natural product alcohol which display its potential as a late-stage functionalization tool.Futher,we promote the application of this protocol to get anti-HIV drug Darunavir and cholesterol involved to afford a complex drug linkage molecule,which forward extend its opportunity as a bioactive molecule linkage tool.In Chapter 3,with the fulfillment of oxonium ylide involved asymmetric aminomethylation,we forward employ the electrophile activation strategy into an enantioselective Rh(II)/chiral phosphoric acid co-catalyzed trapping of indole and diazo ketone derived zwitterion active intermediate with 1,3,5-triazine to afford chiral tryptamine derived compounds.This protocol is the first chiral phosphoric acid dual hydrogen bonding directed zwitterion involved asymmetric aminomethylation.