Study On Palladium-catalyzed Asymmetric Allylation Reaction Of 3-aminooxindoles For The Synthesis Of 3-allyl-3-aminooxindoles

Objective:To establish the palladium-catalyzed regio-and stereoselective allylation reaction system of 3-aminooxindoles for structurally diverse synthesis of chiral 3-allyl-3-aminooxindoles,and to efficiently inrich the synthetic methodologies of 3-substituted-3-aminooxindoles compounds.Methods:?1?To develop the asymmetric allylation reaction system of 3-aminooxindole with 1,3-diphenylallyl acetate in high regioselectivity and stereoselectivity via screening key factors of asymmetry induction including catalysts of palladium complex,chiral ligands and substrate substituents in essential position.?2?Having established optimal conditions,in order to synthesize outstanding enantioselective chiral 3-allyl-3-aminooxindole compounds,we next examine the substrate scope and generality of 3-aminooxindole with 1,3-diphenylallyl acetate,and through difunctionalization of amino and allyl to accomplish transformations of product,structure of abundant chiral 3,3-disubstituted oxindoles derivatives were synthesized.?3?Desired molecules is determined by NMR,HRMS and X-ray single crystal diffraction datasd and figures.The Enantionmeric excesses?ee?values were determined by HPLC analysis with a Chiralpak OD-H,The diastereo ratio?dr?values determined by ¹H NMR integration.Results:?1?The optimal asymmetric allylation reaction system was established successfully,it including 3-aminooxindole?0.1 mmol,1 equiv?,1,3-diphenylallyl acetate?0.15 mmol,1.5 equiv?,[?³-C₃H₅ClPd]₂?5 mol%?,?R?-BINAP?10 mol%?,LiHMDS?1equiv?,TMSCl?1.5 equiv?,DCM?2 mL?at 25 ^oC under N₂ atmosphere.?2?21 examples of structurally diverse chiral 3-allyl-3-aminooxindoles compounds were synthesuzed under the optimal reaction condition,and the isolated yield of products was high to 98%,ee values and dr values was high to 97%and 4:1.?3?Biologically active chiral3,3-disubstituted oxindoles were synthesized by transformations of product.Conculusion:Developed a strategy of asymmetric allylation reaction in the study,which amino and allylic can be introduced at C3 position of oxindoles at the same time,and transformations of product can be used to synthesize others novel chiral 3,3-disubstituted oxindoles derivatives.The strategy have increased transition metals-catalyzed asymmetric synthesis methods with 3-Aminooxindole as starting materials,which theoretically provide a basis designing new asymmetric synthesis methodologies.