Synthesis Of Bifunctional Chiral Phase-Transfer Catalysts And Their Application To Asymmetric Reaction

Three kinds of novel bifunctional phase-transfer catalysts and some known phasetransfer catalysts were synthesized in this thesis. These catalysts were applied to asymmetric fluoronation of β-ketoester and nitro-Mannich reaction.This thesis contains three chapters as following:1. We prepared the first quaternary ammounium type catalysts bearing squarmide donors, including cinchona alkaloids, amino acids and anti-cyclohexyl-diamine skeletons. One of the catalysts derived from quinine was applied to asymmetric fluorination of β-keto esters, high yields with moderate to good enantioselectivity(56-76% ee) were obtained. We have also demonstrated that the squaramide moiety and quaternary ammonium center were crucially important to achieve the moderate and good enantioselectivity, so this catalytic system is bifunctional.2. We prepared the first quaternary ammounium type catalysts bearing multiple hydrogen-bonding donors derived from cinchona alkaloids and various β-aminoalchols. Two catalysts derived from quinine, L-phenylglycinol and quinidine, Dphenylglycinol were found to be highly efficient for nitro-Mannich reaction of α-amidosulfones, very broad substrates scope were observed, we also proved that multiple hydrogen-bonding strategy can mitigate the adverse effect of pseudoenantiomeric nature of cinchona alkaloids, both enantiomers of the products were achieved in highly enantio- and diastereoselectivity(90-99% ee, 13:1-99:1 dr), respectively. We have also demonstrated that the multiple hydrogen-bonding donor moiety and quaternary ammonium center were crucially important to achieve the excellent selectivity, so this catalytic system is bifunctional.3. We prepared four known phase-transfer catalysts and eight new catalysts derived from quinine. Among of the eight catalysts, seven of which contain urea group, one contain thiourea group. Pyridine-2-sulfinamide was obtained through two steps from commercially available 2-thiopyridine, other four methyl pyridine-2-sulfinamide were obtained through three steps from commercially available methyl 2-bromopyridine, quinoline-2-sulfinamide was obtained through three steps from commercially available 2-chloroquinoline. Six novel N-sulfonyl imines were obtained by condensation of above-mentioned sulfonamides with acetophenone followed by oxidation with m-CPBA. We found that N-sulfonyl imine derived from 2-bromo-6-methypyridine was the best substrate considering the yield and ee values of corresponding product in nitro-Mannich reaction. Next, we optimize the reaction conditons detailedly, including catalysts, base, temperature, concentration and solvent. During the process of the optimization of catalysts, we found that the urea donor moiety and quaternary ammonium center in the catalyst were crucially important to achieve the excellent selectivity, so this catalytic system is bifunctional. We also found that catalyst bearing thiourea group can give better catalytic performance than the corresponding one bearing urea group. The reaction was performed at-30 ℃ for 48 h, the product was obtained in 95% yield with 93% ee.