树状结构金鸡纳碱催化剂的合成

手性催化剂负载和回收一直是非常活跃的研究课题。纳米尺寸的树状分子是重要的催化剂载体,具精确、可控的三维结构及特殊的物化性能等特点。金鸡纳碱催化剂在不对称双羟基化、Mannich反应、Diels-Alder等不对称催化反应中有广泛的应用。以不同代数的树状结构的苄醇、1,4-二氯-2,3-二氮杂萘、二氢奎尼丁为原料经烷基化以较高收率制得树状结构金鸡纳碱催化剂,为探讨该类催化剂在不对称催化反应中的催化性能及分离回收奠定了基础。     

有机催化靛红亚胺不对称Mannich反应

手性3-氨基-2-吲哚酮骨架化合物在药物合成领域具有潜在应用价值。目前靛红亚胺参与不对称Manich反应是合成手性3-氨基-2-吲哚酮衍生物的有效方法之一。结合国内外近3年的文献报道,围绕着金鸡纳碱及其衍生物不对称催化、其他有机小分子不对称催化和有机金属不对称催化3个方面综述了靛红亚胺参与的不对称反应合成手性3-氨基-2-吲哚酮衍生物类化合物的研究进展。并对靛红亚胺参与的不对称催化合成3-氨基-2-吲哚酮骨架化合物进行了展望。     

金鸡纳碱衍生物分类

金鸡纳碱衍生物是高效的有机手性催化剂或手性配体,本文根据金鸡纳碱与桥环连接键的类型及桥环类型不同对金鸡纳碱衍生物进行分类。     

金鸡纳碱类催化剂在MBH酯的不对称烯丙基烷基化反应中的应用进展

含有手性中心的结构单元被广泛应用于天然产物和药物活性分子(如羟吲哚、苯并呋喃等)中,展现出广泛的生物活性。由于空间位阻等因素的存在,含有立体手性中心(特别是季碳中心)的结构不易合成。MBH酯容易发生烯丙位的取代反应而构建新的碳碳键受到了广泛的关注,烯丙基烷基化反应一般具有条件温和,操作简单,适用性强的特点,金鸡纳碱衍生物是一种在有机化学中广泛应用的手性辅助剂,也是最常用于此类反应的有机催化剂。本论文主要综述了金鸡纳碱类催化剂在MBH酯的不对称烯丙基烷基化反应中的应用。     

Betti碱及其衍生物的研究进展

本文综述了近年来Betti碱及其衍生物在不对称合成、手性辅助合成以及拆分中的应用，并对未来Betti碱及其衍生物的应用作了展望。     

金鸡纳生物碱衍生物催化的不对称Aza-Michael加成反应

将金鸡纳生物碱衍生物催化剂用于不同查尔酮和苯胺及其衍生物的不对称Aza-Michael加成反应,以65%~92%的化学产率和最高达81%e.e.的对映选择性得到R-构型加成产物。     

双功能有机硫脲催化剂在不对称合成中的应用

综述了双功能有机硫脲催化剂的发现,及其在Michael加成反应、Mannich反应及其它不对称合成反应中的应用,并展望了其应用前景。     

有机催化β-酮酸酯不对称α-羟基化反应研究进展

手性α-羟基β-酮酸酯是多种天然产物及医药产品的重要中间体,获得这一类结构单元最简单的方法是β-酮酸酯的直接不对称α羟基化,因此该反应在医药工业和精细化工领域具有重要的研究价值。本文针对小分子金鸡纳碱衍生物、二萜类生物碱、芳氧基氨基醇及手性相转移催化剂直接氧化β-酮酸酯不对称α-羟基化反应研究,该反应的催化机理被认为是氢键、π-π键等多种分子间力协同作用,同时还需要适当的位阻基团遮蔽以获得羟基化反应立体选择性。     

樟脑及其衍生物—不对称合成中理想的手性助剂

介绍了樟脑及其衍生物在不对称还原反应、加成反应、烷基化反应、Diels-Alder 反应、氧化反应和卤化反应中的应用。同时还列举了樟脑及其衍生物在不对称合成中用作手性试剂和手性催化剂的一些例子。     

手性修饰催化剂在多相不对称氢化中的研究进展

手性修饰金属催化剂是最具发展潜力的多相不对称催化剂之一。本文综述了近年来三个具有代表性的多相不对称氢化反应体系的研究进展,即酒石酸修饰镍催化剂催化β-酮酯不对称加氢体系、金鸡纳生物碱修饰铂催化剂催化α-酮酯不对称加氢体系以及金鸡纳生物碱修饰钯催化剂催化C=C和C=N双键不对称加氢体系。概述了催化体系的影响因素,探讨了酒石酸及金鸡纳生物碱修饰型催化剂的手性识别机理模型。指出开发高效催化剂,修正或提出手性识别机理模型仍是今后多相不对称催化氢化反应研究的方向。     

The Physico-chemical Properties of Cinchona Alkaloids Responsible for their Unique Performance in Chiral Catalysis

The physico-chemical properties of cinchona alkaloids have been characterized in connection to their use for catalytic enantioselective conversions. Adding to the previous identification of their active site at the nitrogen atom in the quinuclidine ring and the chiral environment provided by the carbon centers of the neighboring alcohol linker, an argument is made here for the importance of the adoption of certain rotational conformations by those cinchona alkaloids in optimizing their chiral promotion. Because catalysis with cinchona alkaloids involves a liquid phase, there is a dynamic conformation isomerization process controlled by a number of factors having to do with the exact structure of the cinchona as well as with the nature of the solvent used and, in the case of heterogeneous catalysis, the presence of a solid surface. Solvents of intermediate polarity have been found to be the best for dissolving the cinchona, for establishing rapid adsorption equilibria with metal surfaces, and for promoting chiral catalysis. Protonation also leads to a dramatic change in performance, locking the cinchona molecule in a specific conformation held in place by the counter anion of the acid used, and modifying the chemical and biological activity of the system. Comparative studies with several cinchona indicate that molecular groups attached to peripheral positions also exert a great influence on the conformational and adsorption behavior of these molecules.     

Asymmetric organic catalysis with modified cinchona alkaloids

Insights into the role played by modified cinchona alkaloids in the Sharpless asymmetric dihydroxylation inspired studies of modified cinchona alkaloids as chiral organic catalysts that lead to the development of highly enantioselective alcoholyses for the desymmetrization, kinetic resolution, and dynamic kinetic resolution of cyclic anhydrides, cyanation of ketones, and 1,4-addition of thiols to cylic enones. These studies demonstrate the potential of modified cinchona alkaloids as broadly useful chiral organic catalysts for asymmetric synthesis.     

The direct catalytic asymmetric mannich reaction

The direct catalytic asymmetric addition of unmodified carbonyl compounds to preformed or in situ-generated imines has emerged as a promising new route to optically enriched alpha- and beta-amino acid derivatives, beta-lactams, and 1,2- and gamma-amino alcohols. The direct catalytic asymmetric Mannich reactions are mediated by small organometallic and organic amine catalysts that can achieve levels of selectivity similar to those possible with natural enzymes. The different small-molecule catalysts described here are complementary in their applications. They also complement each other in syn or anti selectivity of the direct asymmetric Mannich reaction. In this Account, we highlight the recent developments in and contributions to this research.     

Organocatalytic Asymmetric Mannich Reactions of 5H‐Oxazol‐4‐ones: Highly Enantio‐ and Diastereoselective Synthesis of Chiral α‐Alkylisoserine Derivatives

The first organocatalytic Mannich reaction of 5H‐oxazol‐4‐ones with various readily prepared aryl‐ and alkylsulfonimides has been developed. Two commercially available pseudoenantiomeric Cinchona alkaloids‐derived tertiary amine/ureas have been demonstrated as the most efficient catalysts to access the opposite enantiomers of the Mannich products with equally excellent enantio‐ and diastereoselectivities. From the Mannich adducts, important α‐methyl‐α‐hydroxy‐β‐amino acid derivatives, such as the α‐methylated C‐13 side chain of taxol and taxotere, can be conveniently prepared.     

Enantioselective hydrogenation of ethyl pyruvate with colloidal platinum catalysts: the effect of acidity on rate

Platinum sols, prepared from H₂PtCl₆ in aqueous methanol, are, when modified by cinchona alkaloids, highly reproducible catalysts for the enantioselective hydrogenation of ethyl pyruvate. It is shown that the presence of HCl in the as-prepared sols has a marked effect on rate and reproducibility, and that removal of HCl by dialysis gives catalysts which display exceptional reproducibility and higher rates. The reliability of these colloidal catalysts will allow their use as a reliable test system both for precise rate studies, in the absence of possible support effects, of the various reaction parameters which affect catalyst performance in this reaction, and also for screening of alternative modifiers to cinchona alkaloids. This revised version was published online in July 2006 with corrections to the Cover Date.     

Hydrogenation of (E)-2-methyl-2-butenoic acid over cinchona-modified Pd catalyst in the presence of achiral amines: Solvent and modifier effect

The effect of the solvent, modifier structure and concentration on the enantioselective hydrogenation of (E)-2-methyl-2-butenoic acid over Pd/Al₂O₃ modified by cinchona alkaloids was influenced by the addition of achiral amines to the reaction slurry. The solvent dependence in the presence of achiral amines showed that additives are involved in the rate determinant step of the reaction, whereas the effect of the dilution pointed to the presence of the acid dimers in the intermediate responsible for enantioselection. The dependence of the enantioselectivity on the cinchonidine concentration in the presence of amines and results obtained using cinchona derivatives and mixtures thereof were in line with our earlier assumptions related to the participation of the amine additive in the formation of the surface intermediate. Based on these and previously published results possible structures of this intermediate are suggested.     

Transient behavior of the enantioselective hydrogenation of a hydroxymethylpyrone

Various 2‐pyrone derivatives are important intermediates in the synthesis of biologically active compounds. Pd chirally modified by cinchona alkaloids has a potential in the enantioselective hydrogenation of 4‐hydroxy‐6‐methyl‐2‐pyrone to the corresponding 5,6‐dihydropyrone. A study of various parameters (solvent, temperature, pressure, concentration) and catalyst systems (Pd/alumina and Pd/titania, modified by cinchonidine or cinchonine) revealed striking variations of the reaction rate and enantioselectivity with conversion. This transient behavior is interpreted by the effect of competitive adsorption and hydrogenation of the substrate and modifier. This revised version was published online in August 2006 with corrections to the Cover Date.     

芳香醛和芳香胺参予的Mannich反应及其合成应用

研究了芳香胺和芳香醛参予的Ｍａｎｎｉｃｈ反应及其合成应用，以它们的原料合成了１０余种新的Ｍａｎｎｉｃｈ碱，也使Ｍａｎｎｉｃｈ反应由单一甲醛扩展到芳香醛，产率为６２．３％～９０．４％。     

Construction of Adjacent Quaternary and Tertiary Stereocenters by Conjugate Addition Using Polymer-Supported Cinchona Alkaloids as Catalysts

Abstract  

A series of polymer-bound cinchona alkaloids has been prepared. The resultant polymer-bound cinchona alkaloids have been used as the catalysts for the asymmetric Michael reaction of 1,3-dicarbonyl compounds and N-benzylmaleimide. The corresponding asymmetric Michael addition product, the first example of adjacent quaternary and tertiary stereocenters synthesized in the presence of a polymer-bound catalyst, has a selectivity of up to 86% ee. Besides, immobilized alkaloid V retains stereochemical reactivity even after being recycled for six times.     

Rigid cinchona conformers in enantioselective catalytic reactions: new cinchona‐modified platinum catalysts in the Orito reaction

The use of cinchona alkaloids (cinchonidine, cinchonine, quinine, quinidine, α-isocinchonine, α-isoquinidine, γ-isoquinidine) in the Orito reaction (hydrogenation of ethyl pyruvate and ethyl benzoylformate) strongly supports the structure of the intermediate complex (cinchona alkaloid “anti‐open” conformer–pyruvate 1 : 1 complex); in addition, so far unknown stereochemical conditions have been identified and the utilization of rigid cinchona conformers in the study of asymmetric syntheses have been generalized. This revised version was published online in July 2006 with corrections to the Cover Date.