Research On Modular Synthesis Of Chiral Oxazoline Ligands And Their Application In Asymmetric Catalysis

Metal complexes catalyzed asymmetric reaction is an important method for modernchiral synthesis. The development of excellent new ligands and highly efficientstereoselective reactions is currently an important topic in metal catalysis. Modular ligandsynthesis as a new idea for design and synthesis of chiral ligands has obtained greatdevelopment. In this thesis, based on the literature survey, under the guidance of the theoryof modular synthesis, we have designed and synthesized a series of chiral ligands, andapplied them in various asymmetric reactions. The main work is as following:Using chiral amino acids and amino alcohols as initial raw materials, through few stepof reaction，chiral2-aminomethyl oxazoline and amino oxazoline modules with differentsubstituents were prepared. Then, these modules reacted with dimethyl squarate or1,1’-binaphthalenyl-3,3’-dicarbaldehyde, a total of13chiral mdular oxazoline ligands wereprepared. These chiral ligands can be readily prepared and possess high modular nature,which facilitates the fine-tuning of structure and catalytic activity.C2-symmetric squaramide-linked bisoxazoline Zn(OTf)2complexes have beenapplied in enantioselective Friedel-Crafts reaction of indoles with,-unsaturated-ketoesters, and the corresponding alkylation products were obtained in good to excellentyields (up to98%) with high enantioselectivities (up to94%ee). A possible transition statemodel was proposed. This enantioselective protocol provides a practical and efficientaccess to indole derivatives bearing a chiral tertiary carbon center and ketoester functionalgroups, which expanded the application field of indole derivatives. This is the first report ofthe application of squaramide oxazoline ligands in asymmetric catalytic reactions.A series of chiral squaramide-linked bisoxazoline ligands and monooxazoline ligandswere synthesized and applied to the Cu(II)-catalyzed asymmetric direct-chlorination ofβ-keto esters and amides, the corresponding chlorination products were obtained inexcellent yields with moderate enantioselectivities under mild conditions. The effect ofsolvent, temperature, Lewis acid and different ligand structure on the enantioinduction wasinvestigated and a possible transition state model was proposed. This was the firstinvestigation of catalytic asymmetric-chlorination of-keto amides. This study hashighlighted that a simple chiral squaramide-oxazoline with cheap Cu(OAc)2·H2Ocomplexes can catalyze this chlorination reaction. We have tried a series of other asymmetric catalytic reactions, such as Henry reaction,Fluorination, Michael addition and cascade reaction, to explore the application of thesechiral modular oxazoline ligands.