Synthsis Of Novel N,O-ligands And Their Applications In Constructing Pyrrolidinyl-Spirooxindoles

The pyrrolidinyl-spirooxindole scaffolds are the core of numerous natural alkaloids with diverse bioactivity profiles. This thesis mainly focused on the synthesis of novel N,O-bidentate Ligands and their applications in constructing pyrrolidinyl-spirooxindoles. Specifically including the following aspects:1. Synthesis of novel N,O-ligands based on1,2-dihydroimidazoleN,O-ligands L1/L2with the structure of1,2-dihydroimidazole pyridine were synthesized in moderate yield employing oxazolidone as chiral source. Meanwhile, N,O-ligands L3based on benzothiazole and quinolone derivative L4were also accomplished, respectively.2. The application of N,O-ligands in constructing pyrrolidinyl-spirooxindoles.After preliminary screening, the N,O-Cu(OAc)2derived chiral complex was demonstrated as an efficient catalyst for asymmetric1,3-dipolar cycloaddition of3-Methyleneoxindole with azomethine ylides, affording the adducts with75/25dr, and the major product in94%ee.The catalytic enantioselective1,3-dipolar cycloadditions of3-benzylideneoxindole with azomethine ylides were developed with N,O-Cu(OAc)2derived chiral complex, providing exo-pyrrolidinyl-spirooxindole compounds in47-99%yields and90-97%ee. Furthermore, the same reaction was accomplished with N,O-AgOAc derived chiral complex affording the same adducts with high86/14-99/1dr and68-89%ee.3. The screening of N, O-ligands in asymmetric1,3-dipolar cycloaddition of nitroethenamineFour chiral center products were obtained in good yields and high enantioselectivities (up to94%ee) under prensent condition.