trans-3-(N,N-dimethylamino)-4-<(trimethylsilyl)ethynyl>-2-azetidinone | 134905-52-5

• 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-3-(N,N-dimethylamino)-4-<(trimethylsilyl)ethynyl>-2-azetidinone
• 英文别名: trans-3-(N,N-dimethylamino)-4-[(trimethylsilyl)ethynyl]-2-azetidinone；(3S,4S)-3-(dimethylamino)-4-(2-trimethylsilylethynyl)azetidin-2-one
• CAS: 134905-52-5
• 化学式: C₁₀H₁₈N₂OSi
• 分子量: 210.351
• InChiKey: TXZYBPGVSBWBBT-IUCAKERBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N,N-二甲基甘氨酸甲酯 、 3,N-bis(trimethylsilyl)propargylamine 生成 trans-3-(N,N-dimethylamino)-4-<(trimethylsilyl)ethynyl>-2-azetidinone
  参考文献：
  名称：

  A new and efficient route to 3-amino-2-azetidinones via zinc enolates of N,N-disubstituted glycine esters

  摘要：

  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.

  DOI：

  10.1021/jo00017a030

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.