trans-1-benzyl-3-(N,N-diethylamino)-4-phenyl-2-azetidinone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: trans-1-benzyl-3-(N,N-diethylamino)-4-phenyl-2-azetidinone
• 英文别名: (3S,4S)-1-benzyl-3-(diethylamino)-4-phenylazetidin-2-one
• 化学式: C₂₀H₂₄N₂O
• 分子量: 308.423
• InChiKey: AUKKDZORHNNHBU-OALUTQOASA-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：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-苄烯丁胺 、 苯亚甲基甲胺 生成 trans-1-benzyl-3-(N,N-diethylamino)-4-phenyl-2-azetidinone
  参考文献：
  名称：

  由烯醇锌和亚胺选择性形成1,3,4-三取代和3,4-二取代的反式-β-内酰胺

  摘要：

  据报导一种高产率合成（最好是90％以上）的反式-β-内酰胺类化合物（azetidin-2-ones）的新方法，该方法涉及α-氨基酸酯烯醇锌与适当的亚胺的1：1反应。该反应可以作为“一锅法”合成进行，正如合成反式-3-二乙基氨基-4-苯基氮杂环丁烷-2-酮所证明的那样（93％收率）。由于分子内螯合物的配位，新型的烯醇锌很可能具有Z-几何形状。已经获得的证据是，在第一步中，这些烯醇锌以高度非对映选择性的方式与亚胺反应，提供苏式醛缩醛酸酯，在随后的步骤中将其闭环成氮杂环丁烷-2-酮。

  DOI：

  10.1002/recl.19871060910

文献信息

• A new and efficient route to 3-amino-2-azetidinones via zinc enolates of N,N-disubstituted glycine esters
  作者：Fred H. Van der Steen、Henk Kleijn、Johann T. B. H. Jastrzebski、Gerard Van Koten

  DOI：10.1021/jo00017a030

  日期：1991.8

  This report describes novel and efficient ''one-pot'' syntheses of 1-unsubstituted-3-amino-4-substituted-2-azetidinones (8 and 9) involving the in situ preparation of lithium and particularly zinc enolates (5 and 6, respectively) of N,N-disubstituted glycine esters (4) and subsequent reactions of these enolates with (simple) imines (7). Lithium enolates 5 only react with activated imines that are N-substituted with an electron-withdrawing group (e.g. aryl, trialkylsilyl), affording cis-3-amino-2-azetidinones in excellent yields with moderate to good stereoselectivity (de 68-92%). Zinc enolates 6 are more generally applicable since they react with activated imines as well as unactivated imines (e.g. those which are N-substituted with an electron-donating group such as alkyl) to afford 3-amino-2-azetidinones in excellent yields. The trans diastereoselectivity of the zinc-mediated enolate-imine condensation can be tuned by changing the steric and electronic properties of the substituents of the reagents (i.e. both enolate and imine), as well as the solvent polarity. The observed stereoselectivities are explained in terms of two highly ordered transition states, consisting of a Z-zinc ester enolate and an E-imine. Protection of the amino function of the metal enolates as a 2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentane ring affords 2-azetidinone products that can be easily deprotected to provide a free 3-amino function. In this way, trans-1-benzyl-3-(protected amino)-4-methyl-2-azetidinone (9a) and trans-3-(protected amino)-4-[(trimethylsilyl)ethynyl]-2-azetidinone (9g), key intermediates in the synthesis of Aztreonam (and 9g for bicyclic beta-lactam antibiotics as well), have been prepared in excellent yields (98 and 93%, respectively) with a high diastereoselectivity (de 82 and 94%, respectively). Furthermore, depending on the reactivity of imines 7, our method is also applicable using a catalytic amount (10 mol %) of ZnCl2.
• Selective formation of 1,3,4-trisubstituted and 3,4-disubstituted trans-β-lactams from zinc enolates and imines
  作者：Johann T. B. H. Jastrzebski、Fred H. van der Steen、Gerard van Koten

  DOI：10.1002/recl.19871060910

  日期：——

  synthesis (better then 90%) of exclusively trans-β-lactams (azetidin-2-ones) is reported which involves the 1:1 reaction of an α-aminoacid ester zinc enolate with an appropriate imine. The reaction can be carried out as a ‘one-pot’ synthesis as has been demonstrated for the synthesis of trans-3-diethylamino-4-phenyl azetidin-2-one (93% yield). The novel zinc enolates have most likely a Z-geometry as a result

  据报导一种高产率合成（最好是90％以上）的反式-β-内酰胺类化合物（azetidin-2-ones）的新方法，该方法涉及α-氨基酸酯烯醇锌与适当的亚胺的1：1反应。该反应可以作为“一锅法”合成进行，正如合成反式-3-二乙基氨基-4-苯基氮杂环丁烷-2-酮所证明的那样（93％收率）。由于分子内螯合物的配位，新型的烯醇锌很可能具有Z-几何形状。已经获得的证据是，在第一步中，这些烯醇锌以高度非对映选择性的方式与亚胺反应，提供苏式醛缩醛酸酯，在随后的步骤中将其闭环成氮杂环丁烷-2-酮。