Asymmetric Catalysis With Metalated Azomethine Ylides

Metalated azomethine ylides are important synthetic intermediates to construct chiral containing-nitrogen heterocycles,which has been widely used for the synthesis of various highly functionalized and enantioenriched pyrroles,imidazoles as well as piperidines.On the other hand,metalated azomethine ylides can be also employed as nucleophiles for the construction of chiral nonproteinogenic α-amino acids.In last decade,our group has always worked on asymmetric catalysis merging metalated azomethine ylides with an array of dipolarophiles or electrophiles,and has achieved good progress.In order to further extend the applications of this containing-nitrogen1,3-dipolars in asymmetric catalysis field,we successfully employed novel synthetic strategies in developing a series of asymmetric catalysis reactions,and the main contents are as followed:1)A highly enantioselective desymmetrization of prochiral cyclopentenediones via Ag(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of metalated azomethine ylides has been successfully developed.The methodology provides facile access to a series of highly functionalized bicyclic pyrrolidine/cyclopentane derivatives in good to high yields with excellent stereoselectivities.2)A highly efficient Ag(I)-catalyzed atroposelective desymmetrization of N-(2-tbutylphenyl)maleimide via 1,3-dipolar cycloaddition of in situ generated metalated azomethine ylides has been successfully established,affording a series of biologically important and enantioenriched octahydropyrrolo[3,4-c]pyrrole derivatives in generally high yields with excellent levels of diastereo-/enantioselectivities.3)We have successfully developed a highly efficient kinetic resolution of racemic cyclopentene-1,3-diones with in situ generated metalated azomethine ylides enabled by a chiral Ag(I)/TF-Bipham Phos complex.This novel methodology works well with a broad substrate scope,affording an array of synthetically important cyclopentene-1,3-diones accompanied by the fused pyrrolidine derivatives with high functionalities.Meanwhile,this strategy allows facile access to the key intermediates for the synthesis of(+)-madindolines A and B.4)An unprecedented asymmetric allenylic alkylation of readily available imino esters enabled by a synergistic Cu(I)/Pd(0)catalysis has been developed.This dual catalytic system possesses good substrate compatibility,delivering a diverse array of nonproteinogenic α-allenylic α-mono-or α,α-disubstituted a-amino acids(α-AAs)with high yields and generally excellent enantioselectivities.Furthermore,the scalability and practicability of the current synthetic protocol were highlighted in the gram-scale reactions and the first catalytic asymmetric synthesis of naturally occurring(S)-α-allenic α-amino acid,respectively.