Study On High Stereoselective Synthesis Of Spiro[Pyrrolidine-3,3'-oxindole]

A copper-catalyzed asymmetric 1,3-dipolar cycloaddition using alkyl substituted 3-methylene-2-oxindoles as dipolarophiles and glycine iminoesters as azomethine ylide precursors has been reported.By using Do novo design of P-stereogenic phosphine ligands developed by our groups,the natural-product-inspired spiro[pyrrolidin-3,3'-oxindole]s are generated in good to excellent yields with high asymmetric induction.And the loading of catalyst as low as 0.1 mol % proves to be highly efficient.The DFT calculations suggests the second Michael addition of the 1,3-dipole to be the rate-and enantiodetermining step.Remarkably,this reaction represents the first example of a highly enantioselective metal catalyzed 1,3-dipolar cycloaddition using azomethine ylide derived from alkyl aldehyde.Moreover,our catalyst system proves to be specifically efficient to promote the synthesis of MDM2-p53 precursor,which is a new class of antiproliferative agents against cancer cell lines,in moderate yield with excellent ee value.