Novel Ferrocenyl Heterocyclic Propanol Chiral Ligand Design, Synthesis And Catalytic Asymmetric Reactions In Applied Research

In this thesis, thirty novel enantiopure ferrocenyl aziridino alcohols as chiral ligands were designed and synthesized from readily available natural L-amino acids. The systematic studies on these chiral ligands possessing only one central chirality, two central chiralities and C2-symmetrical axial chirality were carried out for the application in the catalytic asymmetric addition of diethylzinc to arylaldehydes. An optimized 'one-pot' procedure for the synthesis of iV-ferroc-enylmethylaziridine-2-carboxylic ester from L-serine ester were developed.1. The synthesis of chiral ferrocenyl aziridino alcohol ligands with one stereogenic carbon and their application in the asymmetric catalysisChiral ligands 6a-j were prepared from essily available L-serine 1 by the esterification, condensation, reductive alkylation, cyclization, then reduction with LiAlH4 or treatment with RMgX. All twelve kinds of novel compounds were characterized by 1HNMR, 1CNMR, IR, HRMS and elemental analysis. The specific rotation of compounds 4, 5 and 6 were recorded. The ee of 5, 6e and 6j was determined by HPLC analysis using a chiral column (Chiralcel OD) and was more than 99%. Compounds 5,6e and 6j was further characterized by X-ray diffraction. The X-ray structure analysis revealed that an intramolecular hydrogen bond is present in the compounds 6e and 6j. The chiral ligands 6a-j were used as catalyst to promote the asymmetric addition of diethylzinc to arylaldehydes affording the corresponding 1-aryl-l-propanol in up to 98.8 % enantiomeric excess with high to excellent yields (71-100%). The effect of the ligand structures on the enantioselectivity of reaction was then examined. The results suggested that the hindrance of both the ferrocenyl group and the alcohol moiety of the catalyst played an important role in the enantioselectivity of reaction. A plausible mechanism for catalyzation was proposed and discussed in detail.2. The synthesis of chiral ferrocenyl aziridino alcohol ligands with two stereogenic carbons and their application in the asymmetric catalysisStarting from essily available L-threonine, another ten chiral ligands 12a-j were prepared by the similar to route of 6. The difference between routes of 12 and 6 is the methods for the aziridine ring close. The effect of new substitute on the aziridine ring and newly formed stereogenic carbon on the reactivity and enantioselectivity of reaction was investigated in the asymmetric addition of diethylzinc to arylaldehydes.It was shown that the introduction of methyl group has great effect on the enantioselectivity , but the absolute configuration of the product was not affected bythe new generated central chirality. In the optimized condition, the reaction of diethylzinc with arylaldehydes gave the corresponding alcohols in 100% chemical yields and up to 84% ee.3. The synthesis of chiral ferrocenyl aziridino alcohol ligands with C2-asymmetry and their application in the asymmetric catalysisTen novel chiral C2-asymmetric 1,1 -disubstituted ferrocenyl aziridino alcohol ligands 21a-j were synthesized and characterized by 1HNMR, 1CNMR, IR, MS andelemental analysis, respectively. The structure of compounds 21j was further confirmed by X-ray diffraction. The crystal structure of compounds 21j revealed that a C2-symmetric chiral axis existed in the crystalline state. The chiral ligands 21a-j were used to catalyzed the reaction of diethylzinc with arylaldehydes, and the preliminary results showed that C2-symmetric ligands 21a-j, except 21f and 21j, afforded higher enantioselectivity than ligands 6a-j, respectively. The steric hindrance near the hydroxyl moiety had significant effect on the enantioselectivity. In the presence of 6% of 21e, up to 92.6% ee was obtained in this test reaction. This result suggested that the matching of axial and central chiralities was essential for obtaining excellent asymmetric induction and also demonstrated that the axial chirality was important.