Copper(?)/RuPHOX-Catalyzed Enantioselective Mannich-Type Reaction Of Glycine Schiff Bases With Cyclic Ketimines

As an effective method for constructing C-C and C-N bonds,Mannich reaction is characterized by high efficiency,atomic economy and wide applicability,and is an important method for synthesizing amino acid compounds.On the other hand,transition metal copper has the advantages of rich crust content,low toxicity and low cost,so the asymmetric Mannich reaction catalyzed by copper has received extensive attention.However compared with aldimines,copper-catalyzed asymmetric Mannich reaction of ketimine using glycine ester as nucleophilic reagent to furnish chiral C~?-tetrasubstituted?,?-diamino acid precursors has been rarely reported.In response to this situation,the paper has carried out the following works:Part I:A Cu(?)/RuPHOX-catalyzed enantioselective Mannich-type reaction of glycine Schiff bases with cyclic ketimines was developed,affording chiral?,?-diamino acid derivatives in good yields with moderate to good ees and drs,which provided an efficient methodology for furnishing chiral C~?-tetrasubstituted?,?-diamino acid precursors.The catalytic system is compatible with a series of substrates.In addition,an interesting nonlinear effect of the catalyst's enantiomeric composition on reaction enantioselectivity was observed.Part II:The indolizines is a very important biomolecular skeleton,but there are only a few related asymmetric catalysis researches.In this part,a Co(?)/Box-catalyzed enantioselective addition reaction of indolizines with ketimines was developed,affording chiral tertiary amine containing indolizines structure derivatives in good yields with moderate ees.In summary,in this paper,ketimine was used as a substrate,developing different catalytic systems containing Copper(?)/RuPHOX and Co(?)/Box,to synthesized chiral amine compounds with glycine Schiff bases and indolizines as nucleophiles respectively.