| Chirality is a common feature owned by substances at different levels. According to their basic chiral factors, chiral compounds can possess elements of central, axial, planar and helical chirality. Because many physiological functions themselves are asymmetric, chiral molecules play an important role in science and technology, in particular the ones whose life activities depend on the molecules. So for chemists both in industrial or academic field, it is a major challenge to looking for a truly effective method for obtaining optically pure products. The asymmetric catalytic reaction provide an ideal way to increase molecular chirallity value, that is, a small amount of precisely designed chiral catalyst can promote non-chiral substrate to stereoselectively produce a large number of chiral compounds. As a result, since the second half of the20th century, homogeneous asymmetric catalytic reaction has rapidly attracted the increasing interest of chemists, which lead to more in-depth studies on chiral catalyst. Among all the chiral compounds, the planar chiral compounds such as ferrocene and [2.2]paracyclophane have been widely used in asymmetric catalytic reactions as chiral ligands because of their unique structure. Compared to ferrocene,[2.2]paracyclophane has received more considerable attention since they are easier to be modified and more stable.In recent years, the asymmetric catalytic reactions are carried out in two major directions:the first one is the asymmetric reduction and oxidation of C-C double bond as well as the asymmetric oxidation of C-O or C-N double bond. The research in this direction has been applied into some important industrial synthesis of chiral organic fine chemicals. The second one is to build C-C bond with high stereoselectivity. The comparatively successful reactions include the asymmetric Aldol reaction, the Diels-Alder reaction, as well as the asymmetric addition reaction of aldehyde and ketone with organic Inetal reagent. We choose the second asymmetric catalytic reactions as our main research.For the above reasons, and our interests in [2.2]paracyclophane chemistry and asymmetric catalytic reactions, we comprehensively studied the chemical properties o(?) various kinds of derivatives of [2.2]paracyclophane. At first, we discovered the racemization of planar chiral4-bromo-13-amino[2.2]paracyclophane in dediazoniation reactions. Then we designed and synthesized a series of schiff base ligands and phosphine ligands based on [2.2]paracyclophane, and managed to apply them in Cu-catalyzed asymmetric Henry reaction and Rh-catalyzed asymmetric1,4-addition reaction.The main content of the thesis includes the following aspects:1. Review of the synthesis of the planar chiral ligands based on [2.2]paracyclophane and their application in asymmetric catalytic reactions.With one substituent introduced to the benzene ring of its backbone, the [2.2]paracyclophane ligand can form planar chirality, whose introduction of chirality is easier. Due to the three-dimensional aromaticity of their backbones, this kind of compounds has a higher chemicai resistance to acid, alkali, heat, oxidation, reduction and so on, and their backbones are not easy to be racemized.(generally racemization occurs when the temperature is higher than200℃) So in asymmetric catalytic reactions, the three-dimensional structure can offer a good asymmetric environment to work well.Planar chiral [2.2]paracyclophane-based ligand possesses the characteristic that its backbone structure is made up of a rigid [2.2]paracyclophane unit, which provides the possibility of designing various types of planar chiral ligands. By far, the reported [2.2]paracyclophane-based ligands include all kinds of N, P, O-type ligands such as diphosphine, oxazoline-phosphine, imidazolium, triazolium, oxazoline-phenol, schiff base and so on. They play an increasingly important role in asymmetric catalytic reactions such as hydrogenation, hydrosilylation, epoxidation, cyclopropanation and boration.2. Dediazoniation reactions of4-bromo-13-[2.2]paracyclophanyl diazonium fluoborate:insight into a mechanism of unexpected racemization.In previous studies, our group has proven that4-bromo-13-amino [2.2]paracyclophane is a versatile building block for synthesis of planar chiral [2.2]paracyclophane-based ligands with substituents on both rings. We optimized and improved the systhesis method of this compound to make the operation easier and the yield higher. Since amino could be transformed into hydroxy, cyano, thiocyanate, fluorine and iodine by dediazoniation reactions, the spatial structure of4-bromo-13-amino[2.2]paracyclophane can be modified easily. In these reactions, we discovered that different products had different levels of racemization. It is known that the chiral [2.2]paracyclophane backbone is chemically and configurationally stable under ambient conditions. The thermal racemization is possible only upon cleavage of the ethano-bridge at about200℃. This incredible discovery led to our in-depth study on their mechanism of racemization. By comparing different amino[2.2]paracyclophanes, we confirmed that only planar chiral4-bromo-13-amino[2.2]paracyclophane can be racemized. And by comparing different mechanisms of dediazoniation reactions, we concluded that the mechanism of racemization of bromonium cation was formed through bromine migration induced by the carbonation. Based on the results, not only we can make a qualitatively judgment on the mechanism of dediazoniation reactions,(It can be judged from whether the products are racemized or racemization levels), to provide the most powerful proof, but also we can make a quantitative calculation of the reaction kinetics and obtain the reaction rate.3. A series of schiff base ligands based on [2.2]paracyclophane backbones were synthesized and separated. The planar chiral [2.2]paracyclophane schiff bases were used as ligands in Cu-catalyzed asymmetric Henry reaction with high yield and enantioselectivity.(up to96%ee value)Schiff base ligands are an important class of ligands for asymmetric catalytic reactions, and their good coordination and stability play a significant role. Based on the previous studies and references, we synthesized a new family of schiff base ligands with central and planar chirality, and employed them in Cu-catalyzed asymmetric Henry reaction with high yield and enantioselectivity. We improved our previous catalytic conditions and evaluated the substituent effects of diverse substituents on the13-position of the [2.2]paracyclophane. 4. A series of diphosphine ligands based on [2.2]paracyclophane were designed and synthesized. The planar chiral [2.2]paracyclophane diphosphines were used as ligands in Rh-catalyzed asymmetric1,4-addition reaction with high yield and enantioselectivity.(up to91%ee value)Rh-catalyzed asymmetric1,4-addition reaction of aryl boronic to cyclohexenone has been studied more thoroughly, and this kind of reaction has the following features: at first, since the organic boric acid used in the reaction is very stable both in the air and water, the reaction can be carried out in the protic solvent or the aqueous solution which lead to the simple operation; moreover, no rhodium, neither1,4-addition reaction nor1,2-addition reaction occurs. And this characteristic of rhodium is not owned by other organometallic reagents; finally, as Rh-catalyzed system can work in mild condition and has a large number of substrates, it has been widely used. In addition, the catalyst for this reaction is the compound generated by rhodium and phosphine ligand. And the phosphine ligand is one of the most studied and the most widely used ligands, so we have many options.Little has been reported about diphosphine ligands based on [2.2]paracyclophane except for PHANEPHOS and its derivatives. However, based on the4-bromo-13-hydroxy[2.2]paracyclophane, various kinds of hydioxy-phosphine compounds were synthesized by P-Fries rearrangement reation. And according to the weak coordination of alkoxyl group, different types of alkoxyl diphosphine ligands were also obtained. In addition to these, we also employed [2.2]paracyclophane diphosphines as ligands in Rh-catalyzed asymmetric1,4-addition reaction with enantioselectivity of up to91%.The main innovation of this thesis is the discovery of the racemization of4-bromo-13-amino[2.2]paracyclophane in the dediazoniation reactions and the explanation of its mechanism, providing the most direct proof for the mechanism study. Another innovation is the synthesis of a series of schiff base ligands based on [2,2]paracyclophane by Fries rearrangement reaction, and their application in Cu-catalyzed high enantioselective Henry reaction. The third innovation is the synthesis of a series of diphosphine ligands based on [2.2]paracyclophane by P-Fries rearrangement reaction, and their application in Rh-catalyzed high enantioselective1,4-addition reaction. |
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