Modifications And Immobilization Of Chiral Silver Catalysts For Asymmetric 1,3-Dipolar Transformations Of Glycine-derived Schiff Bases

Substituted pyrrolidine derivatives are widely found in natural products and biologic molecules,and the pyrrolidine is an important skeleton fragment in pharmaceutical and organic chemistry research.Meanwhile,1,3-dipolar cycloadditions have been proved to be one of the most facile and practical approaches for the construction of chiral pyrrolidine structure or ?-amino acid derivatives.And numerous reports have demonstrated that azomethine yelides derived from glycine are one of the most commonly used 1,3-dipoles,which has a privileged ability to give various kinds of multi-substituted chiral pyrrolidine by 1,3-dipolar [3+2]cycloaddition with EWG-activated alkenes.In this thesis,in order to further expand the application value of glycine-derived 1,3-dipoles,we investigated the silver-catalyzed asymmetric transformation from the perspective of designing new reactions and immobilizing the chiral silver catalytic systems for the catalytic asymmetric 1,3-diploar addition.Notably,there is no reported example that focused on the enantioselective [3+2]cycloaddition of glycine aldimino esters with unsymmetrical EWG-activated alkenes bearing two different carbonyl groups.To resolve this problem,a unique 1,3-dipolar[3+2] cycloaddition of alkyl 4-oxo-4-arylbut-2-enoates bearing two different electron-withdrawing groups was successfully determined using a silver/(R)-DTBM-Segphos catalyst system,which gives the corresponding fully substituted pyrrolidines containing four stereogenic centers with excellent enantioselectivities(up to 98% ee).And then,we explored new method for the immobilization of chiral silver-based catalyst system.And based on numerous experimental results,it was found that the chiral silver catalytic system could be successfully fixed in silicone elastomer,taking advantage of the swelling performance of silicon rubber and a small amount of hydrosilane(Si-H)functional groups that could be used to react with silver salt to turn the silver salt to possible nanosilver.Further investigations shows that the silicone elastomer fixed chiral silver catalyst can be repeatedly used for 1,3-dipolar additionsinvolving two types of compounds: MBH acetate and dicarbonyl-activated olefins.For example,in the 1,3-dipolar [3+2] cycloaddition of alkyl4-oxo-4-arylbut-2-enoates and azomethine yelide,the silver catalyst in silicon rubber could be recyclable up to 3 times without any obvious decrease in yields.Furthermore,up to 5 times catalyst recycle was successfully observed for the conjugate addition-elimination reaction of azomethine yelide with MBH acetate.These experimental results showed that new method with silicon rubber as a support for asymmetric silver-catalyzed 1,3-dipolar addition is useful for the recycled use of chiral silver catalyst.