The Application Of Chiral Heteroarylidene-tethered Bis(Oxazoline) And Bis(Thiazoline) Ligands In Asymmetric Catalysis

During the past decades the asymmetric catalysis has been extensively developed, and is still one of the most powerful research areas to date. The asymmetric catalysis afforded a solid theoretical foundation for the chiral parmaceuticals, pesticides and other chemical products. The development of new chiral catalyst is one of the major topics in asymmetric catalysis.In our previous studies, the heteroarylidene-tethered bis(oxazoline) ligands explored by us demonstrated excellent catalytic behavior in the asymmetric Friedel-Crafts alkylation of indoles. In this thesis, we further investigated the application of these bis(oxazoline) ligands in other asymmetric catalytic reaction. In addition, we have synthesized a series of heteroarylidene-tethered bis(thiazoline) ligands, and investigated their application in the asymmetric reactions.First, asymmetric Friedel-Crafts amidoalkylation of indoles with N-sulfonyl imines was realized using the heteroarylidene-tethered bis(oxazoline) ligand L6-Cu(OTf)2complex. The reaction proceeded smoothly under mild conditions to afford the adducts in good yields and enantioselectivities (70～90%yield, up to>99%ee). Compared with the previously published Evans’bis(oxazoline) ligand lc-Cu(OTf)2complex, our catalyst provided better reactivities and comparable enantioselectivities in most cases.Second, the ligand Ll-Cu(OTf)2complex was used in the asymmetric Friedel-Crafts alkylation of indoles with β, γunsatirated a-ketoesters. Compared with the previously published catalysts, better enantioselectivities and yields were obtained (81～99%yield, up to>99%ee). In addition, it is the first time to realize the asymmetric Friedel-Crafts alkylation of unprotected pyrrole with β, γ-unsaturated a-ketoesters in good yield with high enantioselectivity (87-99%yield, up to92%ee). Furthermore, the inversion of the pyrrole adduct configuration was realized by the L4-Cu(OTf)2complex (up to98%ee).Third, using heteroarylidene malonate and chiral amino alcohols as starting materials, a family of heteroarylidene-tethered chiral bis(thiazoline) ligands were prepared via six-step reactions. Their application in the asymmetric Friedel-Crafts alkylation of indoles with arylidene malonates was investigated (55～99%yield, up to99%ee). The reactivity was slightly lower than that of the corresponding bis(oxazoline) analogues.We have also investigated the application of these ligands in other asymmetric catalysis, such as allylic alkylation, F-C alkylation of indoles with nitroalkenes and Henry reaction, and so on.In summary, this thesis disclosed a relatively systematic studies on the application of the heteroarylidene-tethered bis(oxazoline) and bis(thiazoline) ligands in asymmetric catalysis. Among those reactions, some displayed much better catalytic results than the previously reported methods. This work provided theoretical direction and experimental basis for the development of new chiral catalysts and catalytic methods.