A New Trifluoromethylated Sulfonamide Phosphine Ligand For Ag(?)-Catalyzed Enantioselective [3+2] Cycloaddition

Highly substituted pyrrolidine derivatives are prevalent in natural products,biologic and pharmaceutical molecules.Furthermore,it is also a privileged architecture in chiral ligands and organocatalysts.Catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides with electron-deficient alkenes is one of the most powerful and diversity oriented synthetic methods for theconstruction of this type of compounds.It is still highly desirable to develop new catalyst systems,especially ones with efficient and simple chiral ligands for asymmetric 1,3-dipolar cycloaddition reactions compatible with broad functional groups for the synthesis of multi-substituted pyrrolidine derivatives.Over the past few years,Ming-Phoses of chiral sulfonamide phosphine ligands,have been successfully applied to Cu(I)-catalyzed asymmetric [3+2] cycloaddition reactions of azomethine ylides with ?-trifluoromethyl-?,?-disubstituted enones and ?-trifluoromethyl-?,?-unsaturated esters with excellent diastereo-and enantioselectivity.A newly developed Ming-phos ligand((S,Rs)-M8)with 3,5-bis(trifluoromethyl)phenyl substituent was demonstrated to be highly efficient for Ag-catalyzed asymmetric [3+2] cycloaddition reactions of azomethine ylides with maleimides.Being easily prepared on scale in one step,the ligand in combination with Ag catalyst enables the synthesis of a variety of highly functionalized bicyclic pyrrolidine derivatives in good yields and excellent enantioselectivities under mild conditions.The desymmetrization process of prochiral N-(2-t-butylphenyl)maleimide allowed for the access of the octahydropyrrolo[3,4-c]pyrrole derivatives decorated with four adjacent stereogenic centers and one N-C chiral axis.Based on the above work,we used Ag(I)/Ming-Phos complex as an effective catalyst for atroposelective desymmetrization of prochiral cyclopentene-1,3-diones with azomethine ylides,affording bicyclic pyrrolidine derivatives decorated with four adjacent stereogenic centers and one quaternary carbon center through 1,3-dipolar cycloaddition reaction.