催化不对称傅-克反应研究进展

催化不对称傅-克反应是构建具有光学活性芳基化合物最有效的方法之一。自从1877年报道了首例傅-克反应后,该反应得到化学家们的关注。最近二十年,许多手性双功能有机小分子催化剂（如金鸡纳碱、手性脯氨醇硅醚、手性磷酸、手性硫脲等）以及金属与手性配体（如手性双氮氧、手性双唑啉、手性席夫碱）形成的配合物催化剂被应用到各类不对称傅-克反应中。本文主要从反应的芳基底物类型分类,对近年来酚、吡咯、呋喃以及噻吩参与的不对称傅-克反应进行简要概述,同时对这类反应所存在的问题和局限性进行总结,并对今后发展方向作了展望。     

基于三氟甲基砌块的催化不对称傅-克反应研究进展

引入三氟甲基基团可以显著提高有机分子的化学和代谢稳定性、亲脂性以及在细胞膜中的渗透性,因此发展高效合成三氟甲基化合物,特别是手性三氟甲基化合物的方法具有非常重要的意义.基于三氟甲基砌块的催化不对称傅-克反应可以高效高选择性获得手性三氟甲基芳香化合物,是最近发展起来的一个研究热点.自从日本Mikami小组采用手性钛络合物研究了首例基于三氟甲基砌块的催化不对称傅-克反应,不同种类的手性有机金属催化剂(如手性钛,铜,锌,锆,钯,镱,钇,镍,钙等金属络合物)和手性有机小分子催化剂(如金鸡纳碱,手性脯氨醇硅醚,手性磷酸等)都在这类不对称催化反应中得到应用.作者主要对反应组分(特别是不同类型的三氟甲基砌块)、反应条件、反应机理和合成应用等方面的研究进行了综述.最后,对这类反应所存在的问题和局限性进行了总结,并对今后发展方向作了展望.     

合成(R)-(+)-N,N-二甲基-1-二茂铁基乙胺的方法改进

二茂铁与乙酰氯经傅-克反应制得乙酰基二茂铁(1);1在Ru(Ⅱ)-(R,R)-TsDPEN催化下完成不对称氢转移制得手性仲醇(3);3酯化后再与二甲胺通过亲核取代反应合成了光学活性的(R)-(+)-N,N-二甲基-1-二茂铁基乙胺,总产率54.5%,其结构经1H NMR和IR确证。     

不对称傅-克反应在构建手性3-取代吲哚中的研究进展

由于手性3-取代吲哚化合物是许多具有生物活性天然产物和药物分子的核心骨架,其合成方法的研究就格外令人注目.尤其是近二十年来,利用手性金属配合物和有机小分子催化剂实现吲哚的C(3)位不对称傅-克烷基化反应已成为有机界广泛研究的热点.按照促进不对称傅-克烷基化反应的手性催化剂进行分类,就近年来其在3-取代吲哚化合物合成中的应用加以综述,并对今后的发展方向进行了展望.     

傅-克酰基化反应的机理及动力学研究进展

总结了傅-克酰基化反应提出以来,化学工作者对该反应的机理方面的研究,包括动力学研究、中间体结构和性质的.提出傅-克反应机理目前存在的疑问及机理动力学的发展方向.     

有机催化吲哚与环状酮亚胺膦酸酯的傅-克反应合成含手性季碳胺基膦酸衍生物

在有机合成中,季碳中心的构建始终是一项充满挑战的课题.含手性季碳中心的胺基膦酸化合物以其多样的生物活性,如酶抑制剂、抗真菌剂、抗菌剂和抗病毒剂等,受到了科研工作者的广泛关注.目前已有许多合成策略报道,其中亲核试剂与α-酮亚胺膦酸酯的不对称加成策略为含手性季碳中心胺基膦酸衍生物的合成提供了一条简洁有效的路径,但是却鲜有报道,已有的报道也仅局限于乙酰氰、丙酮、硝基甲烷和芳基硼酸作亲核试剂.为满足多样的手性胺基膦酸衍生物的合成需求,新的合成策略和亲核源仍有待进一步发展.值得一提的是,不对称傅-克反应是一种非常有效的构建碳-碳键的合成方法,并已有广泛报道.基于吲哚与亚胺底物的傅-克反应经验,我们研究组发展了一种有机催化吲哚与环状酮亚胺膦酸酯傅-克反应合成含手性季碳胺基膦酸衍生物的方法,使用的有机催化剂是手性磷酸.通过对溶剂、催化剂和温度的筛选发现,使用在3,3′-位引入吸电子的3,5-二三氟甲基苯基取代的H8-BINOL衍生的手性磷酸作催化剂,反应温度为30 oC,溶剂为均三甲苯时,最高能以98%对映选择性得到含手性季碳胺基膦酸酯化合物.该反应操作简单,条件温和,不仅适用于吲哚衍生物,对吡咯也能取得较好结果.总之,该方法提供了一条简洁有效的合成手性胺基膦酸衍生物的途径.     

手性膦小分子催化不对称反应的研究进展

手性膦小分子催化的不对称反应是目前研究的热点之一,该类反应具有反应时间短、条件温和、催化活性高、环境友好等优点,符合绿色化学发展方向.对手性膦小分子催化的不对称Morita-Baylis-Hillman反应、Morita-Baylis-Hillman加成物的烯丙基位立体选择性取代反应、环加成反应、酯化反应,γ-加成反应以及其它重要的不对称反应进行简要的评述.     

有机小分子催化的不对称Strecker反应研究进展

有机小分子催化的不对称合成反应是目前研究最为活跃的领域之一. 不对称Strecker反应是合成光学活性α-氨基酸衍生物的有效手段. 目前报道的催化不对称Strecker反应的有机催化剂主要有手性胍类、手性(硫)脲衍生物、氮-氧偶极化合物、手性Brønsted酸等, 取得了良好的催化活性和对映选择性. 对各类有机小分子催化剂在有机催化不对称Strecker反应中的应用研究进展, 以及催化剂结构与反应条件对催化活性和不对称诱导作用的影响进行了简要评述.     

硫酸亚铈催化的芳香化合物与苄基醇、烯丙醇类化合物以及苄基氯的傅-克烷基化反应研究

硫酸亚铈作为一种便宜的和有效的催化剂催化芳香化合物与苄基醇、烯丙醇类化合物和苄基氯的傅-克烷基化反应. 在1～10 mol%的硫酸亚铈存在下, 芳香化合物分别与苄基醇、烯丙醇类化合物和苄基氯能够顺利有效地进行傅-克烷基化反应. 此外, 催化剂能回收, 再次使用三次也没有明显地失去催化活性.     

C2对称性有机小分子催化的高对映选择性Aldol反应

以环己酮与4-硝基苯甲醛直接不对称Aldol缩合为模型反应,对一系列具有C2对称性的有机小分子催化剂进行了考察,其中(2S,5S)-吡咯烷-2,5-二羧酸的不对称催化效果最好.在10℃下,以DMSO为溶剂,30%摩尔分数催化剂用量,研究了多个取代芳香醛和环己酮的不对称催化Aldol反应,对映选择性为87%～99?.     

Catalytic Asymmetric Hetero-Diels-Alder Reactions of Carbonyl Compounds and Imines

Asymmetric catalysis is a challenge for chemists: How can we design catalysts to achieve the goal of forming optically active compounds? This review provides the reader with an overview of the development of catalytic asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines. Since its discovery, the Diels-Alder reaction has undergone intensive development and is of fundamental importance for synthetic, physical, and theoretical chemists. The Diels-Alder reaction has been through different stages of development, and at the beginning of the 21st century catalytic Diels-Alder reactions are one of the main areas of focus. The preparation of numerous compounds of importance for our society is based on cycloaddition reactions to carbonyl compounds and imines. There are several parallels between the reactions of carbonyl compounds and those of imines, which, however, begin to vanish on entering the field of catalytic reactions. Why? From a mechanistic point of view some similarities can be drawn, but the synthetic development of catalytic enantioselective hetero-Diels-Alder reactions of imines are several years behind those of the carbonyl compounds. For hetero-Diels-Alder reactions of carbonyl compounds there a number of different chiral catalysts, and great progress has been achieved in developing enantioselective reactions for unactivated and activated carbonyl compounds. In contrast the development of catalytic enantioselective hetero-Diels-Alder reactions of imines is in its infancy and only few catalytic reactions have been published. This review will focus on the most important developments, and discuss the synthetic and mechanistic aspects of enantioselective hetero-Diels-Alder reactions of carbonyl compounds catalyzed by chiral Lewis acids. For the hetero-Diels-Alder reactions of imines, the diastereoselective reactions of optically substrates catalyzed by Lewis acids will be presented first, followed by the catalytic enantioselective reactions.     

Catalytic enantioselective fluorination of oxindoles

We have developed a highly efficient catalytic enantioselective fluorination of oxindole derivatives. In the presence of a catalytic amount of chiral Pd complex 2 (2.5 mol %), various substrates, including aryl- and alkyl-substituted oxindoles, were fluorinated in a highly enantioselective manner (up to 96% ee). In addition, when R was a hydrogen atom, enantioselective fluorination followed by solvolysis gave a monofluorinated ester with up to 93% ee. To our knowledge, this is the first example of catalytic enantioselective fluorination of oxindoles.     

Asymmetric Synthesis in Ionic Liquids

Summary. In the last decades catalytic enantioselective transformations have became one of the most studied fields in synthesis chemistry. With the advancement of biphasic catalysis several of these reactions have been adapted to be run in ionic liquids. The variability of ionic liquids provides the means to fine tune catalytic processes, and even more importantly, the ionic liquids might be used to immobilize the catalyst and allow its easy recycling. The present review aims to provide an overview of the state of the art of enantioselective homogeneous catalytic transformations in ionic liquids.     

Asymmetric Synthesis in Ionic Liquids

In the last decades catalytic enantioselective transformations have became one of the most studied fields in synthesis chemistry. With the advancement of biphasic catalysis several of these reactions have been adapted to be run in ionic liquids. The variability of ionic liquids provides the means to fine tune catalytic processes, and even more importantly, the ionic liquids might be used to immobilize the catalyst and allow its easy recycling. The present review aims to provide an overview of the state of the art of enantioselective homogeneous catalytic transformations in ionic liquids.     

Catalytic Enantioselective Synthesis of Helicenes

Helicenes and helicene-like molecules, usually containing multiple ortho-fused aromatic rings, possess unique helical chirality. These compounds have found a wide range of important applications in many research fields, such as asymmetric catalysis, molecular recognition, sensors and responsive switches, circularly polarized luminescence materials and others. However, the catalytic enantioselective synthesis of helicenes was largely underexplored, when compared with the enantioselective synthesis of molecules bearing other stereogenic elements (e.g. central chirality and axial chirality). Since the pioneer work of asymmetric synthesis of helicenes via enantioselective [2+2+2] cycloaddition of triynes by Stará and Starý, last two decades have witnessed the tremendous development in the catalytic enantioselective synthesis of helicenes. In this review, we comprehensively summarized the advances in this field, which include methods enabled by both transition metal catalysis and organocatalysis, and provide our perspective on its future development.     

Chemoselective and enantioselective oxidation of indoles employing aspartyl peptide catalysts

Catalytic enantioselective indole oxidation is a process of particular relevance to the chemistry of complex alkaloids, as it has been implicated in their biosynthesis. In the context of synthetic methodology, catalytic enantioselective indole oxidation allows a rapid and biomimetic entry into several classes of alkaloid natural products. Despite this potentially high utility in the total synthesis, reports of catalytic enantioselective indole oxidation remain sparse. Here we report a highly chemoselective catalytic system for the indole oxidation that delivers 3-hydroxy-indolenines with good chemical yields and moderate to high levels of enantio- and diastereoselectivity (up to 95:5 er and up to 92:8 dr). These results represent, to our knowledge, the most selective values yet reported in the literature for catalytic asymmetric indole oxidation. Furthermore, the utility of enantioenriched hydroxy-indolenines in stereospecific rearrangements is demonstrated.     

Catalytic asymmetric cyanosilylation of ketones with chiral Lewis base

The development of broadly applicable and practical catalytic approaches for the enantioselective creation of quaternary stereocenters remains a highly desirable yet challenging goal. In this Communication, we describe a highly enantioselective cyanosilylation of acetal ketones (alpha,alpha-dialkoxy ketones) catalyzed by modified cinchona alkaloids. This reaction is the first highly enantioselective cyanosilylation of ketones catalyzed by an organic chiral Lewis base and is found to be highly efficient with acetal ketones bearing a broad range of alkyl, aryl, alkenyl, and alkynyl substituents. This new catalytic asymmetric reaction, coupled with the versatility of the acetal functionality, provides a broadly useful synthetic method for chiral building blocks bearing quaternary stereocenters. Acetal ketones, readily accessible but previously unexplored in asymmetric synthesis, demonstrate unusual reactivity and selectivity toward the nucleophilic cyanosilylation, thereby suggesting that they may be interesting substrates for other catalytic enantioselective reactions.     

Rich chemistry of nitroso compounds

Nitrosobenzene or nitrosopyridine are found to be attractive electrophiles in catalytic enantioselective carbon-nitrogen and/or carbon-oxygen bond forming reactions. In the presence of designer Lewis or Br?nsted acid catalysts, catalytic enantioselective O- and N-nitroso aldol reaction or nitroso Diels-Alder reaction proceed smoothly. The scope and limitation of new catalytic processes are described.     

Enantioselective organocatalytic three-component Petasis reaction among salicylaldehydes, amines, and organoboronic acids

The catalytic enantioselective three-component Petasis reaction among salicylaldehydes, amines, and organoboronic acids with a newly designed thiourea-binol catalyst is presented. A broad range of alkylaminophenols can be obtained in good yield (up to 92%) and good to high enantioselectivity (up to 95% ee). A possible reaction pathway for this catalytic enantioselective Petasis reaction is tentatively proposed.     

Chiral Organocatalysts in Enantioselective CO2 Utilization Reactions

The development of efficient CO₂ utilization reactions has gained a significant amount of attention in recent years. Although transformations of CO₂ to produce basic chemicals have been extensively investigated, the development of catalytic enantioselective CO₂ utilization reactions for the preparation of fine chemicals remains limited at this stage. Several excellent methods for catalytic enantioselective CO₂ utilization using chiral metal complex catalysts have been reported. Many researchers have also focused on developing organocatalyzed approaches to enantioselective CO₂ utilization, and several excellent examples have appeared in recent years. Herein, recent advances in catalytic enantioselective CO₂ utilization reactions using chiral organocatalysts are reviewed to provide a forecast for organocatalyzed enantioselective CO₂ utilization research.