(S)-4-(4-nitrophenyl)-4-(4-methoxyphenylamino)butan-2-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-4-(4-nitrophenyl)-4-(4-methoxyphenylamino)butan-2-one
• 英文别名: (4S)-4-(4-methoxyanilino)-4-(4-nitrophenyl)butan-2-one
• 化学式: C₁₇H₁₈N₂O₄
• 分子量: 314.341
• InChiKey: POQWYGCFIVVZJQ-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-(4-甲氧基苯基)-1-(4-硝基苯基)甲亚胺 、 丙酮 在 1,1'-([2,2'-bipyridine]-4,4'-diyl)bis(3-(3,5-bis(trifluoro-methyl)phenyl)thiourea) 、 L-脯氨酸 作用下， 以 甲苯 为溶剂， 反应 24.5h， 以65%的产率得到(S)-4-(4-nitrophenyl)-4-(4-methoxyphenylamino)butan-2-one
  参考文献：
  名称：

  Study of asymmetric aldol and Mannich reactions catalyzed by proline–thiourea host–guest complexes in nonpolar solvents

  摘要：

  A proline-thiourea host-guest complex has been described as a good catalyst for asymmetric reactions such as aldol and Mannich reactions. High stereoselectivities were obtained under optimal conditions. Thiourea was observed to have an important effect on the reactivity and selectivity, even in an unconventional nonpolar reaction medium and without the need to utilize low temperatures. This proline-thiourea host-guest system has the ability to participate in a hydrogen bonding network. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2013.03.014

文献信息

• Organocatalysis in Ionic Liquids: Highly Efficient<scp>l</scp>-Proline-Catalyzed Direct Asymmetric Mannich Reactions Involving Ketone and Aldehyde Nucleophiles
  作者：Carlos F. Barbas III、Naidu S. Chowdari、D. B. Ramachary

  DOI：10.1055/s-2003-41483

  日期：——

  asymmetric Mannich reactions of N-PMP protected a-imino ethyl glyoxylate with various alde- hydes and ketones in ionic liquids afforded both a- and b-amino acid derivatives with excellent yields and enantioselectivities, providing facile product isolation, catalyst recycling, and signifi- cantly improved reaction rates, ca 4- to 50-fold. Three component Mannich reactions involving other imines also

  脯氨酸催化的 N-PMP 保护的 α-亚氨基乙醛酸乙酯与各种醛和酮在离子液体中的直接不对称曼尼希反应提供了具有优异产率和对映选择性的 a-和 b-氨基酸衍生物，提供了容易的产物分离和催化剂回收，并且显着提高了反应速率，大约 4 到 50 倍。涉及其他亚胺的三组分曼尼希反应也适用于离子液体。离子液体溶剂在该反应中的显着优点和局限性已被揭示。
• The Scope of the Direct Proline-Catalyzed Asymmetric Addition of Ketones to Imines
  作者：Wolfgang Notz、Shin-ichi Watanabe、Naidu S. Chowdari、Guofu Zhong、Juan M. Betancort、Fujie Tanaka、Carlos F. Barbas

  DOI：10.1002/adsc.200404114

  日期：2004.8

  A full account of catalytic direct asymmetric Mannich-type reactions is presented describing the scope of amino acid-catalyzed additions of unmodified ketones to a large variety of imines. These reactions are performed under very mild, operationally simple, and environmentally friendly and benign conditions employing a one-pot, three-component protocol as well as preformed imines. Typically, products

  提供了催化直接不对称曼尼希型反应的完整说明，描述了氨基酸催化的未修饰酮加到各种亚胺中的范围。这些反应是在非常温和的，操作简单的，环境友好的和良性的条件下进行的，采用一锅，三组分方案以及预先形成的亚胺。通常，获得的产物具有高区域和非对映选择性以及极好的对映选择性。所开发的方法学被用作合成对映体纯的功能化α-氨基酸，γ-内酯，肟功能化氨基酸以及药理学上重要的靶标（如（R）-环己基甘氨酸）的有力方法。
• Synthesis of a bipyridine-derived achiral thiourea trifluoromethanesulfonic acid salt and its application as an additive in organocatalytic asymmetric reactions
  作者：Ayhan Sıtkı Demir、Sinan Basceken

  DOI：10.1016/j.tetlet.2013.08.004

  日期：2013.10

  The host–guest complex of a proline–thiourea bipyridine trifluoromethanesulfonic acid salt can catalyze organocatalytic asymmetric reactions such as aldol, Michael, and Mannich in polar protic medium with high stereoselectivities. The privileged bipyridine backbone and the thiourea motif are essential to the activity and enantioselectivity through hydrogen bonding interactions.

  脯氨酸-硫脲联吡啶三氟甲烷磺酸盐的主体-客体络合物可以在极性高的质子性质子介质中催化有机催化不对称反应，如羟醛，迈克尔和曼尼希。优先的联吡啶主链和硫脲基序对于通过氢键相互作用的活性和对映选择性至关重要。
• The Proline-Catalyzed Direct Asymmetric Three-Component Mannich Reaction:  Scope, Optimization, and Application to the Highly Enantioselective Synthesis of 1,2-Amino Alcohols
  作者：Benjamin List、Peter Pojarliev、William T. Biller、Harry J. Martin

  DOI：10.1021/ja0174231

  日期：2002.2.1

  We have developed proline-catalyzed direct asymmetric three-component Mannich reactions of ketones, aldehydes, and amines. Several of the studied reactions provide beta-amino carbonyl compounds (Mannich products) in excellent enantio-, diastereo-, regio-, and chemoselectivities. The scope of each of the three components and the influence of the catalyst structure on the reaction are described. Reaction

  我们开发了脯氨酸催化的酮、醛和胺的直接不对称三组分曼尼希反应。一些研究的反应提供了具有出色对映选择性、非对映选择性、区域选择性和化学选择性的 β-氨基羰基化合物（曼尼希产物）。描述了三种组分各自的范围以及催化剂结构对反应的影响。优化了反应条件，讨论了不对称诱导的机理和来源。我们进一步介绍了我们的反应在 1,2-氨基醇的高度对映选择性合成中的应用。
• Poly(Ethylene Glycol)-Supported Proline: A Versatile Catalyst for the Enantioselective Aldol and Iminoaldol Reactions
  作者：Maurizio Benaglia、Mauro Cinquini、Franco Cozzi、Alessandra Puglisi、Giuseppe Celentano

  DOI：10.1002/1615-4169(200207)344:5<533::aid-adsc533>3.0.co;2-y

  日期：2002.7

  (2S,4R)-4-Hydroxyproline has been anchored to the monomethyl ether of poly(ethylene glycol), M-w 5000, by means of a succinate spacer to afford a soluble, polymer-supported catalyst (PEG-Pro) for enantioselective aldol and iminoaldol condensation reactions. This organic catalyst can be considered as a minimalistic version of a type I aldolase enzyme, with the polymer chain replacing the enzyme's peptide backbone, and the proline residue acting as the enzyme's active site. In the presence of PEG-Pro (0.25 - 0.35 mol equiv.), acetone reacted with enolizable and non-enolizable aldehydes and imines to afford beta-ketols and beta-aminoketones in good yield and high enantiomeric excess (ee), comparable to those obtained using non-supported proline derivatives as the catalysts. Extension of the PEG-Pro-promoted condensation to hydroxyacetone as the aldol donor opened an access to synthetically relevant anti-alpha,beta-dihydroxyketones and syn-alpha-hydroxy- beta-aminoketones, that were obtained in moderate to good yields, and good to high diastereo- and enantioselectivity. Exploiting its solubility properties, the PEG-Pro catalyst was easily recovered and recycled to promote all of the above-mentioned reactions, that occurred in slowly diminishing yields but virtually unchanged ee's.

  (2S,4R)-4-羟基脯氨酸通过succinateSpacer键合到分子量为5000的单甲醚聚乙二醇(PEG)上，制备成可溶性、载体化催化剂(PEG-Pro)，用于具有立体选择性的aldol和iminoaldol缩合反应。该有机催化剂可被认为是I型aldol酶的极简版本，其中聚乙二醇链替代了酶的肽主链，脯氨酸残基则充当了酶的活性中心。在PEG-Pro(0.25-0.35mol当量)存在下，丙酮与可烯醇化和不可烯醇化的醛类以及亚胺反应，以良好收率和高对映体过量值得到了β-酮醇和β-氨基酮；其结果与采用非载体化脯氨酸衍生物作为催化剂时所获得的结果相当。将PEG-Pro催化的缩合反应推广到羟基丙酮作为aldol供体，即可获得具有合成价值的anti-α,β-二羟基酮和syn-α-羟基-β-氨基酮；这类产物具有中等到良好的收率，并表现出良好至极佳的双和对映选择性。利用其溶解性能，PEG-Pro催化剂易于回收并循环再利用，可用来推动上述所有反应；这些反应的收率虽逐步减小，但对映体过量值几乎不变。