Synthesis Of Novel Chiral Cyclopropane-Based Bisoxazoline Ligands And Their Asymmetric Induction In Catalytic Asymmetric Reactions

In recent years, chiral bis(oxazolines) ligands with a various of structural diversity have received a great deal of attention through their efficiently use in numerous asymmetric reactions, including cyclopropanation, Diels-Alder, allylic substitution and Michael addition reactions. On the other hand, the cyclopropane-based ligands offering an advantageous combination of structural rigidity and highly variable platform, and unusual bond angles have emerged as efficient ligands in asymmetric reactions such as radical additions, nitrone cycloadditions and allylic alkylation. These results stimulated us to incorporate high constrained dimethylcyclopropane into bis(oxazoline) ligands for discovering an even better metal-oxazoline catalyst. In this dissertation, eight novel bisoxazoline ligands L1-L8 containing 2,2-dimethyl cyclopropane units have been synthesized and evaluated in the asymmetric cyclopropanation and Diels-Alder reaction, moreover the influence of many factors on the enantioselectivity of the new ligands was studied in detail.The cis novel bisoxazoline ligands L1-L4 have been synthesized through the treatment of new cis dihydroxy diamide with p-toluenesulfonyl chloride in the presence of catalytic quantity of 4-(dimethylamino)-pyridine, and the cis dihydroxy diamide could be achieved from the condensation of the amino alcohols and cis cyclopropane dicarbonyl chloride prepared via oxidation and halogenation from cis-2,2-dimethyl-3-formylcyclopropanecarboxylate with DCC. Similarly, the trans novel bisoxazoline ligands L5-L8 have been prepared through the self-cyclization of the new trans dihydroxy diamides same as the cis isomers, which could be easily synthesized from trans cyclopropane dicarbonyl chloride and amino alcohols, and trans cyclopropane dicarbonyl chloride could be prepared from (l R,3R )-ethyl trans -3-formyl-2,2-dimethylcyclopropanecarboxylate as starting material, via oxidation, hydrolyzation and halogenation.In order to evaluate the chiral inducing ability of the prepared ligands L1-L8, the copper-catalyzed cyclopropanation of styrene with ethyl diazoacetate was carried out. All the cis ligands had some extent of asymmetric induction, especially L1 afforded the cis (1R,2S) isomer with the moderate enantioselectivity (53% ee) and trans (1R,2R) isomer with 37% ee , but the trans ligands had weak asymmetric induction. Moreover, the influence of solvent, metal, ligand and molecular sieve on the reaction was also investigated, and the mechanism of new ligand-metal catalysis for cyclopropanation model reaction was proposed according to the conserted mechanism of cyclopropanation by Hofinann.In addition to cyclopropanation, the typical Diels-Alder reaction between cyclopentadiene and N-acryloyl-l,3-oxazolidinine-2-one with Ll-L8/metal complexes have also been studied. All the cis ligands had some extent of enantioselectivity, and the best result from L4 to afford S-endo isomer with 41% ee, however, the trans ligands had poor enantioselectivity. Furthermore, the effects of ligands, metal and reaction time on the reaction were also researched, and the process of new ligand-metal catalysis for Diels-Alder reaction was also analyzed according to Evans' square planar mode and Corey's tetrahedral manner.The seventeen new compounds in the dissertation were characterized by IR, ~1H NMR, ~13C NMR, MS, and elemental analysis or high resolution mass.