路易斯碱催化的烯胺不对称还原研究

手性胺不仅是许多天然产物和手性药物的重要结构单元，而且也是非常有用的拆分试剂、手性配体和手性催化剂。亚胺和烯胺的不对称催化还原是制备手性胺的最直接有效的方式之一，手性有机小分子催化的亚胺不对称还原已取得了很大的进展，但到目前为止，有机小分子催化的烯胺不对称还原极少见文献报道。 本研究以廉价的三氯氢硅为氢源、DMF 等路易斯碱为催化剂实现了烯胺的高效还原。通过反应条件的优化，各种烯胺底物在0.1 eq. DMF 催化下、12 个小时内可以获得非常高的收率（>93%）。 在本课题组前期研究的基础上，我们筛选并设计了一系列以手性哌啶酸和叔丁基亚磺酰胺为母体的有机小分子路易斯碱催化剂，它们能催化三氯氢硅对(Z)-N-苄氧羰基-1-苯基丙烯胺的不对称还原，获得很高的收率和中等的对映选择性，并且具有很好的底物普适性。另外，通过机理方面的研究，我们推测在反应过程中一分子烯胺先捕获一个质子而转变为亚胺正离子，然后受到路易斯碱活化的三氯氢硅中的富电氢原子进攻该亚胺正离子得到还原产物。 另外，本文列出了在此课题进展中所发现的一些新反应，并且试图去阐释这些反应的作用机理。 Catalytic enantioselective reduction of imines and enamines represents one of the most straightforward and efficient methods for the preparation of chiral amines, which are not only important building blocks of many natrural products and chiral drugs, but also can serve as useful resolution reagents, chiral ligands and chiral catalysts. By now, asymmetric reduction of enamines catalyzed by organocatalysts has scarcely been reported, although organocatalyzed enantioselective reduction of imines has already gained great progress. In this study, we report the DMF-catalyzed reduction of enamines with high yields using HSiCl3 as the reducing agent. Under the optimized reaction conditions, various enamines can be reduced in the presence of 0.1 eq. DMF with high yields (>93%) in 12 hours. We screened a set of Lewis base organocatalysts derived from chiral pipecolinic acid and tert-butanesulfinamide for the reduction of (Z)-N-Cbz-1- phenylpropenamine, including newly designed ones and some of those previously developed in our lab. However, only moderate stereoselectivities, albeit high yields were obtained. As for the mechanism, we speculate that the enamine firstly engages a proton to form an iminium species, which is then attacked by the nucleophlic hydrogen of HSiCl3 activated by Leiws base. During the above studies, we have also discovered some new reactions, for which feasible mechanisms were proposed.

苯乙酮、氨甲酸酯参与的直接Mannich反应

Mannich反应是有机化学中最重要的碳-碳键形成反应，其产物是合成手性胺的通用中间体。间接Mannich反应使用不稳定的预制烯醇等当体，以未修饰的酮为给体的直接方法将增强Mannich反应的效率。针对低活性苯乙酮、氨甲酸酯参与的直接Mannich反应，研究工作将更具挑战性。 在前期实验中，我们发现Lewis酸-NbCl5可高效催化苯乙酮、芳香醛、芳香胺三组分直接Mannich反应，反应在环境温度下进行，高收率获得Mannich碱。这是以苯乙酮参与的Mannich反应中，实现催化量Lewis酸催化的首次报道。该方法高效且操作简单。但就底物而言，对易去保护、低活性的氨甲酸酯类底物收率较低。我们设想Brønst酸可解决此类底物问题。令人高兴的是，杂多酸可高效催化芳香酮、芳香醛、氨甲酸酯三组分直接Mannich反应，反应在环境温度下进行，高收率获得N-保护的β-氨基酮。该方法底物范围广泛，普适性强且催化剂便宜。 基于杂多酸在苯乙酮、氨甲酸酯为底物直接Mannich反应中的高效性，我们设想杂多酸与功能化的手性有机小分子-手性伯胺组装可解决催化剂回收问题，同时实现不对称催化。实验结果表明，非共价键固载手性伯胺不能有效催化苯乙酮为底物的直接Mannich反应，无论是对映选择性还是收率均较低。随后，我们以丙二酸酯及α-氨基砜为底物，以增强底物活性，同时绕开亚胺的不稳定性。辛可宁伯胺以氢键双活化底物，有效催化原位产生氨甲酸酯类亚胺与丙二酸酯的Mannich反应，高收率获得Mannich碱，ee值中等。 我们采用逐步解决问题的策略解决Mannich反应中的部分问题并在Lewis酸催化、Brønst酸催化、非共价键固载手性伯胺催化及手性伯胺氢键催化的直接Mannich反应中做出了有益探索。 The Mannich reactions are among the most fundamental carbon-carbon bond forming reactions in organic chemistry, and the reaction products are versatile intermediates in the synthesis of chiral amines. The indirect Mannich reaction uses preformed enolate equivalents. However the preformed enolates are unstable. Thus, a direct methodology based on unmodified ketone donors would enhance the efficiency of the Mannich reaction. Especially researches for the directed Mannich reactions of acetophenone, carbamate, which own lower activities, will be more challengeable. In the initial experiments, we found an efficient Lewis acid-NbCl5 which could catalyze three-component Mannich-type reaction of acetophenone, aromatic aldehydes and aromatic amines at ambient temperature in high yields. This is the first report that use catalytic amount of Lewis acid in the Mannich reactions of .acetophenone. The method reported is not only simple to operate but also efficient. However, as far as amines are concerned, the substrates of carbamates which can be deprotected more easily and less reactive than amines give low yields. We envisaged that Brønsted acid would resolve this problem. Pleasingly, heteropoly acids (HPA) efficiently catalyzed one-pot three-component Mannich reactions of aryl aldehydes, aryl ketones, and carbamates at ambient temperature and afforded the corresponding N-protected β-amino ketones in good to excellent yields. This method provides a novel and improved modification of three-component Mannich reactions in terms of a wide scope of aldehydes, ketones and carbamates, economic viability. Based on the high efficiency of heteropoly acids in the Mannich reaction of acetophenone and carbamates, we envisaged that if HPA were combined with functionalized chiral organocatalysts–chiral primary amines the assemblies may be able to act as recoverable asymmetric organocatalysts. The results of exprimentals showed that noncovalently supported heterogeneous chiral primary amine couldn’t effectively catalyze the Mannich reactions which own two the substrate of acetophenone regardless of enantioselectivity and yield. Then, we employed malonates and α-amido sulfones as substrates to enhance reactivity of substrates and circumvent the instability of imines. A moderately enantioselective and highly yield Mannich reaction with in situ generation of carbamate-protected imines from stable α-amido sulfones catalyzed by cinchonine primary amine catalyst was developed. It is noteworthy that cinchonine primary amine can dual activate substrates through H-bond activation and thus promote the reaction. We applied step-by-step-strategy to resolve some problems in the Mannich reactions and did some instructive explorations in Lewis acid catalysis, Brønst acid catalysis, noncovalently supported heterogeneous chiral primary amine catalysis and chiral primary amine as hydrogen-bond catalysis.

Production of heavy and superheavy nuclei in massive fusion reactions

Within the framework of a dinuclear system (DNS) model, the evaporation-residue excitation functions and the quasi-fission mass yields in the 48Ca induced fusion reactions are investigated systematically and compared with available experimental data. Maximal production cross sections of superheavy nuclei based on stable actinide targets are obtained. Isotopic trends in the production of the superheavy elements Z = 110, 112–118 based on the actinide isotopic targets are analyzed systematically. Optimal evaporation channels and combinations as well as the corresponding excitation energies are proposed. The possible factors that influencing the isotopic dependence of the production cross sections are analyzed. The formation of the superheavy nuclei based on the isotopes U with different projectiles are also investigated and calculated.

Production mechanism of superheavy nuclei in massive fusion reactions

Within the concept of the dinuclear system (DNS), a dynamical model is proposed for describing the formation of superheavy nuclei in complete fusion reactions by incorporating the coupling of the relative motion to the nucleon transfer process. The capture of two heavy colliding nuclei, the formation of the compound nucleus and the de-excitation process are calculated by using an empirical coupled channel model, solving a set of microscopically derived master equations numerically and applying statistical theory, respectively.Fusion-fission reactions and evaporation residue excitation functions of synthesizing superheavy nuclei (SHN)are investigated systematically and compared them with available experimental data. The possible factors that affecting the production cross sections of SHN are discussed in this workshop.