胺甲酰氟促进的镍催化非活化烯烃的不对称胺甲酰基-芳基化反应

过渡金属催化烯烃的不对称双碳官能团化反应提供了一种快速构建手性化合物的简便方法,近年来备受化学研究者们的关注[1].目前主要的研究思路是通过设计含苯环的底物现场生成芳基金属物种,来进行不活泼烯烃的分子内不对称双官能团化反应.对于含有非苯并底物的非活化烯烃的不对称双碳官能团化反应来实现季碳手性中心的构建,已报道的仅有少数通过酰基金属中间体的策略[2-4].2010年,Takemoto等[2]报道了一例钯催化烯烃和胺甲酰氰的不对称胺酰基氰化反应来构建季碳手性中心。     

非官能化烯烃的不对称催化环氧化反应

手性环氧化合物是有机合成的重要中间体,由于三元杂环的张力使其很容易与各种亲核试剂作用,通过官能团转化反应,可以从环氧化物制备一系列不同结构的手性化合物.烯烃的不对称环氧化反应可以使潜手性的烯烃转化为带有手性碳的环氧化合物,在医药、农药、香料等精细化学品的合成上具有非常重要的意义.非官能化烯烃经手性催化剂诱导的不对称环氧化反应是获得光学纯手性化合物的有效方法.这些手性催化剂包括生物酶、金属卟啉、金属Salen配合物以及有机小分子催化剂.本文综述了这几种催化剂催化的非官能化烯烃不对称催化环氧化反应近几年的研究进展,介绍了催化剂的催化机理,并就其发展趋势提出了构想.     

对映选择性亲电氟化反应研究进展

含氟有机化合物, 特别是手性氟化物在医药、农药及功能性材料等相关领域的作用备受注目. 尽管在分子中有立体选择性地引入一个氟原子一直是有机化学家面临的一个挑战性问题, 近年来在化学家们的不断努力下, 对映选择性氟化反应研究取得重要进展. 高光学活性的手性氟化物可通过手性亲电氟化试剂诱导的立体选择性氟化反应, 基于底物的手性氟化反应以及手性催化剂诱导的不对称催化氟化反应等来制备. 特别是, 手性金属配合物和有机催化剂诱导的不对称催化氟化反应被广泛应用于各类手性氟化物的合成, 已成为不对称氟化反应研究的热点. 全面介绍对映选择性亲电氟化反应研究概况和最新进展, 讨论各种不对称氟化反应的特点及应用范围.     

过渡金属催化不对称C-H键官能团化反应构建轴手性联芳基化合物研究进展

在手性分子中,轴手性化合物占据着非常重要的地位.从原子和步骤经济性方面考虑,利用不对称碳-氢官能团化反应构建轴手性化合物是最简洁高效的方法.随着过渡金属催化的不对称碳-氢键官能团化领域的逐步发展,利用该策略来构建轴手性联芳基化合物的研究成果也不断涌现.本文综述了通过过渡金属钯、铑和铱催化的不对称碳-氢键官能团化反应合成轴手性联芳基化合物的最新进展.此外,还介绍了利用这些方法合成多种轴手性配体及其催化的不对称反应,以及这些方法在天然产物合成中的应用.     

手性1,2-二氢吡啶化合物的合成研究进展

手性1,2-二氢吡啶化合物是重要的手性砌块, 可通过还原或环加成反应来方便构建药物分子中十分重要的手性含氮杂环化合物如哌啶等, 因此其高效合成对于新药研发具有重要的研究意义. 利用手性源和手性辅基诱导的策略需要使用化学计量的手性试剂, 发展不对称催化的方法来合成结构多样性的手性1,2-二氢吡啶化合物无疑十分重要. 自2004年报道首例对活化吡啶的不对称C2位亲核加成反应以来, 该策略被成功用于发展合成C2位芳基、烷基、炔基等取代的手性1,2-二氢吡啶化合物的不对称催化新方法. 最近, 一种新的基于亚胺不对称转化的串联反应策略也被设计开发用于多样性合成这类手性含氮杂环化合物. 本综述概述了相关研究进展, 并介绍了相关研究难点和未来的发展空间.     

聚合物负载的手性催化剂和手性试剂的合成及应用

近年来,用聚合物负载的手性催化剂和手性试剂完成的不对称合成反应主要集中在潜手性酮的不对称还原反应;烯烃的不对称双羟基化反应;烯烃的不对称环氧化反应;不对称Diels-Alder反应和饱和碳原子上的不对称取代反应.就近十年来聚合物负载手性催化剂和手性试剂的合成及应用进行了讨论.     

烯烃以糖衍生的手性酮为催化剂的有机催化不对称环氧化

由糖衍生的手性酮是非官能化烯烃的有机催化不对称环氧化的一类重要催化剂,它与过氧硫酸氢钾（KHSO5）可原位产生对顺式烯烃、反式烯烃、三取代烯烃和末端烯烃均有效的氧化剂--手性二氧杂环丙烷.本文对由糖衍生的手性酮的合成方法、不对称诱导反应的机理、手性酮糖的分子结构以及反应条件对其催化活性和不对称诱导作用的影响进行了评述.     

手性磷酸催化的有机催化不对称反应

手性磷酸是近年来发展起来的一类新型高效、高对映选择性的Brønsted酸类有机催化剂, 已成功应用于催化不对称Mannich反应、还原胺化反应、Pictet-Spengler反应、aza-Diels-Alder反应和aza-Ene反应等许多重要的有机合成反应. 手性磷酸催化剂分子内同时含有Lewis碱性位点和Brønsted酸性位点, 可同时活化亲电与亲核底物. 作为一种新型双功能有机催化剂, 手性磷酸具有较高的催化活性和对映选择性, 催化剂最低用量可达0.05 mol%. 对各类手性磷酸催化剂在有机催化不对称合成反应中的应用研究进展, 以及不对称诱导反应的机理、手性磷酸的分子结构及反应条件对其催化活性和不对称诱导活性的影响进行了评述.     

对接-迁移:烯烃的自由基双官能化反应利器

烯烃双官能化反应能同时向烯烃两端引入两个不同官能团,实现简单烯烃向复杂官能化分子的高效转化,一直受到合成化学家的广泛关注.其中自由基介导的烯烃双官能化反应由于具有条件温和、类型多样等特点使其近年来备受关注.对接-迁移策略通过巧妙的双官能化试剂的设计,将自由基供体和迁移基团通过链接基团置于同一分子中,经与烯烃进行对接后再发生快速的分子内官能团迁移而实现烯烃双官能化.该策略针对烯烃底物的兼容范围广,对活化烯烃、非活化烯烃及具有复杂骨架的烯烃都有良好的适用性,为生物活性分子的后期改造提供了便利途径.本文主要综述了本课题组近几年内发展及利用对接-迁移策略实现的烯烃双官能化反应的进展.     

聚合物负载的手性催化剂和手性试剂和合成及应用

近年来,用聚合物负载的手性催化剂和手性试剂完成的不对称合成反应主要集中在潜手性酮的不对称还原反应;烯烃的不对称双羟基化反应;烯烃的不对称环氧化反应;不对称Ｄｉｅｌｓ－Ａｌｄｅｒ反应和饱和碳原子上的不对称取代反应。就近十年来聚合物负载手性催化剂和手性试剂的合成及应用进行了讨论。     

Enantioselective Construction of Axially Chiral Amino Sulfide Vinyl Arenes by Chiral Sulfide‐Catalyzed Electrophilic Carbothiolation of Alkynes

The enantioselective construction of axially chiral compounds by electrophilic carbothiolation of alkynes is disclosed for the first time. This enantioselective transformation is enabled by the use of a Ts‐protected bifunctional sulfide catalyst and Ms‐protected ortho‐alkynylaryl amines (Ts=tosyl; Ms=mesyl). Both electrophilic arylthiolating and electrophilic trifluoromethylthiolating reagents are suitable for this reaction. The obtained products of axially chiral vinyl–aryl amino sulfides can be easily converted into biaryl amino sulfides, biaryl amino sulfoxides, biaryl amines, vinyl–aryl amines, and other valuable difunctionalized compounds.     

Enantioselective Trifluoromethylthiolating Lactonization Catalyzed by an Indane‐Based Chiral Sulfide

Enantioselective trifluoromethylthiolation, especially of alkenes, is a challenging task. In this work, we have developed an efficient approach for enantioselective trifluoromethylthiolating lactonization by designing an indane‐based bifunctional chiral sulfide catalyst and a shelf‐stable electrophilic SCF₃ reagent. The desired products were formed with diastereoselectivities of >99:1 and good to excellent enantioselectivities. The transformation represents the first enantioselective trifluoromethylthiolation of alkenes and the first enantioselective trifluoromethylthiolation that is enabled by a catalyst with a Lewis basic sulfur center.     

Enantioselective Synthesis of Chiral Isotopomers of 1‐Alkanols by a ZACA–Cu‐Catalyzed Cross‐Coupling Protocol

Chiral compounds arising from the replacement of hydrogen atoms by deuterium are very important in organic chemistry and biochemistry. Some of these chiral compounds have a non‐measurable specific rotation, owing to very small differences between the isotopomeric groups, and exhibit cryptochirality. This particular class of compounds is difficult to synthesize and characterize. Herein, we present a catalytic and highly enantioselective conversion of terminal alkenes to various β and more remote chiral isotopomers of 1‐alkanols, with ≥99 % enantiomeric excess (ee), by the Zr‐catalyzed asymmetric carboalumination of alkenes (ZACA) and Cu‐catalyzed cross‐coupling reactions. ZACA‐in situ iodinolysis of allyl alcohol and ZACA‐in situ oxidation of TBS‐protected ω‐alkene‐1‐ols protocols were applied to the synthesis of both (R)‐ and (S)‐difunctional intermediates with 80–90 % ee. These intermediates were readily purified to provide enantiomerically pure (≥99 % ee) compounds by lipase‐catalyzed acetylation. These functionally rich intermediates serve as very useful synthons for the construction of various chiral isotopomers of 1‐alkanols in excellent enantiomeric purity (≥99 % ee) by introducing deuterium‐labeled groups by Cu‐catalyzed cross‐coupling reactions without epimerization.     

Enantioselective C?C and C?H Bond Formation Mediated or Catalyzed by Chiral ebthi Complexes of Titanium and Zirconium

The development of catalytic processes that effect enantioselective bond formation under mild conditions is an important and challenging task in modern chemical synthesis. In this connection, chiral C₂-symmetric ansa-metallocenes (bridged metallocenes) have found notable applications as catalysts. This article discusses the chemistry of this class of chiral metallocene complexes with regard to their utility in catalytic and enantioselective C? C and C? H bond formation reactions. In addition, where applicable, a brief comparison with other related catalytic enantioselective processes is offered. Many of the reactions effected with high levels of enantioselectivity by catalytic amounts of these complexes are of great significance to the preparation of new materials and in the synthesis of therapeutic agents. For example, zirconocene complexes readily catalyze the enantioselective addition of alkylmagnesium halides to alkenes, and cationic zirconocene complexes may promote the highly stereoregulated copolymerization of terminal alkenes. Furthermore, the related chiral titanocenes are involved in an impressive range of useful asymmetric catalytic reactions, including the enantioselective hydrogenation of olefins and reduction of imines or ketones. This review attempts to bring together the practical aspects of the use of [(ebthi)M] complexes of Group 4 transition metals (catalyst synthesis and resolution), outline the manner in which the C₂-symmetric chiral ligands are believed to initiate stereoselective bond formation, and highlight the aspects of this chemistry that are less well understood and require further research.     

Enantioselective Construction of Axially Chiral Amino Sulfide Vinyl Arenes by Chiral Sulfide-Catalyzed Electrophilic Carbothiolation of Alkynes

The enantioselective construction of axially chiral compounds by electrophilic carbothiolation of alkynes is disclosed for the first time. This enantioselective transformation is enabled by the use of a Ts-protected bifunctional sulfide catalyst and Ms-protected ortho-alkynylaryl amines (Ts=tosyl; Ms=mesyl). Both electrophilic arylthiolating and electrophilic trifluoromethylthiolating reagents are suitable for this reaction. The obtained products of axially chiral vinyl–aryl amino sulfides can be easily converted into biaryl amino sulfides, biaryl amino sulfoxides, biaryl amines, vinyl–aryl amines, and other valuable difunctionalized compounds.     

手性配体在钯催化不对称碳氢键活化反应中的应用

目前,手性配体辅助钯催化的区域和对映选择性碳氢键活化是过渡金属催化的前沿领域.在过去的十年中,它作为一种越来越重要的合成工具,用于合成含有各种不对称元素(中心手性、轴手性和平面手性)的手性分子,也是快速构建各种碳碳键和碳杂原子键的最有效方法之一.本文介绍了一些典型手性配体在钯催化不对称sp2和sp3碳氢键活化/官能团化...     

Brønsted Acid Catalyzed Asymmetric Hydroamination of Alkenes: Synthesis of Pyrrolidines Bearing a Tetrasubstituted Carbon Stereocenter

The first highly enantioselective Brønsted acid catalyzed intramolecular hydroamination of alkenes enables the efficient construction of a series of chiral (spirocyclic) pyrrolidines with an α‐tetrasubstituted carbon stereocenter with excellent functional group tolerance. A unique feature of this strategy is the use of a thiourea group acting as both the activating and the directing group through cooperative multiple hydrogen bonding with a Brønsted acid and the double bond. The utility of this method is highlighted by the facile construction of chiral synthetic intermediates and important structural motifs that are widely found in organic synthesis.     

过渡金属催化的有机硼试剂对醛酮的不对称加成研究进展

手性芳基醇是一类重要的合成砌块,广泛存在于许多生物活性分子以及天然产物中,因此,高效高选择性地构建该类化合物是有机化学家们一直关注的研究热点.金属试剂对羰基化合物的不对称加成是构建手性芳基醇的一个简单高效的方法,其中,有机硼试剂由于其方便易得、稳定、低毒、官能团耐受性好等优点而被广泛用于醛、酮的不对称加成反应中.本文综述了过去二十年来过渡金属催化的有机硼试剂对醛、酮的不对称加成反应研究进展,并介绍了一些方法在生物活性手性分子合成中的应用.     

Enantioselective conjugate addition of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones catalyzed by chiral bifunctional organocatalysts

The catalytic enantioselective conjugate addition reaction of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones promoted by chiral bifunctional organocatalysts is described. The treatment of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones under mild reaction conditions afforded the corresponding Michael adducts with high enantioselectivity. The conjugate addition adducts are useful for the synthesis of chiral monofluoromethylated compounds.