cis-(3S,4R)-1(S)-(α-methylbenzyl)-3-<(methoxycarbonyl)amino>-4-ethyl-2-azetidinone | 141040-17-7

• 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: cis-(3S,4R)-1(S)-(α-methylbenzyl)-3-<(methoxycarbonyl)amino>-4-ethyl-2-azetidinone
• 英文别名: methyl N-[(2R,3S)-2-ethyl-4-oxo-1-[(1S)-1-phenylethyl]azetidin-3-yl]carbamate
• CAS: 141040-17-7
• 化学式: C₁₅H₂₀N₂O₃
• 分子量: 276.335
• InChiKey: DCKCSFPCQOLPRX-UHTWSYAYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  cis-(3S,4R)-1(S)-(α-methylbenzyl)-3-<(methoxycarbonyl)amino>-4-ethyl-2-azetidinone 在 氨 、 sodium 作用下， 以 四氢呋喃 为溶剂， 以95%的产率得到cis-(3S,4R)-3-<(methoxycarbonyl)amino>-4-ethyl-2-azetidinone
  参考文献：
  名称：

  Enantioselective synthesis of 3-amino-2-azetidinones via the ester enolate - imine condensation

  摘要：

  Three approaches to the enantioselective synthesis of 3-amino-4-substituted-2-azetidinones by condensation of alpha-amino ester enolates with imines are described: (i) application of chiral ester derivatives of NN-diethylglycine; (ii) application of chiral N-(alpha-methylbenzyl)imines; and (iii) application of chiral imines derived from (2R)-2,3-O-isopropylideneglyceraldehyde. Zinc and aluminum enolates of (-)-menthyl- and (-)-bornyl NN-diethylglycine esters react with simple imines to selectively afford trans-3-(diethylamino)-2-azetidinones, but with a low chiral induction (ee 0-35%). However, reactions of the metal (Li, Zn, Al) ester enolates of (2,2,5,5-tetramethyl-1-aza-2,4-disilacyclopent-1-yl)acetic acid ethyl ester (1c) with N-(alpha-methylbenzyl)imines yield N-protected 3-amino-2-azetidinones in excellent yields and with very high diastereo- and enantioselectivities. The best results are obtained for the zinc-mediated reactions. For example, trans-(3R,4S)-1(R)-(alpha-methylbenzyl)-3-(2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentyl)-4-[N-(R)-(alpha-methylbenzyl)imino]-2-azeti dineone (4a), a fully protected key intermediate (having the unnatural C-3 configuration) for the synthesis of known monobactam and bicyclic beta-lactam antibiotics, was synthesized in 91% yield with an ee of 91%. Application of chiral imines derived from acetaldehyde and propionaldehyde enable, depending on the solvent, the selective high yielding synthesis (de 60-99%; ee >95%) of any one of the four stereoisomers of 3-amino-4-alkyl-2-azetidinones, which are key intermediates for the synthesis of Aztreonam and related antibiotics. In Et2O, a weakly polar solvent, the trans isomers are formed, whereas the use of a polar THF/HMPA solvent mixture results in formation of the cis isomers. Reaction of the zinc enolate of 1c with the N-(4-methoxyphenyl)imine derivative 2i of (2R)-2,3-O-isopropylidene glyceraldehyde affords trans-(3R,4S)-3-amino-4-[(1'S)-1',2'-O-isopropylideneethyl]-2-azetidinone (10a) in excellent yield (de 86%; ee >98%), whereas reaction of the lithium enolate of 1c with the N-(trimethylsilyl)imine derivative 21 affords the cis-(3S,4S) isomer 10d (key intermediate for the synthesis of Carumonam) in good yield (de >90%; >90%). A rationale for the observed stereoselectivities in terms of highly ordered transition states is presented.

  DOI：

  10.1021/jo00040a034
• 作为产物：
  描述：

  cis-(3S,4R)-1(S)-(α-methylbenzyl)-3-(2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentyl)-4-ethyl-2-azetidinone 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 2.0h， 生成 cis-(3S,4R)-1(S)-(α-methylbenzyl)-3-<(methoxycarbonyl)amino>-4-ethyl-2-azetidinone
  参考文献：
  名称：

  Enantioselective synthesis of 3-amino-2-azetidinones via the ester enolate - imine condensation

  摘要：

  Three approaches to the enantioselective synthesis of 3-amino-4-substituted-2-azetidinones by condensation of alpha-amino ester enolates with imines are described: (i) application of chiral ester derivatives of NN-diethylglycine; (ii) application of chiral N-(alpha-methylbenzyl)imines; and (iii) application of chiral imines derived from (2R)-2,3-O-isopropylideneglyceraldehyde. Zinc and aluminum enolates of (-)-menthyl- and (-)-bornyl NN-diethylglycine esters react with simple imines to selectively afford trans-3-(diethylamino)-2-azetidinones, but with a low chiral induction (ee 0-35%). However, reactions of the metal (Li, Zn, Al) ester enolates of (2,2,5,5-tetramethyl-1-aza-2,4-disilacyclopent-1-yl)acetic acid ethyl ester (1c) with N-(alpha-methylbenzyl)imines yield N-protected 3-amino-2-azetidinones in excellent yields and with very high diastereo- and enantioselectivities. The best results are obtained for the zinc-mediated reactions. For example, trans-(3R,4S)-1(R)-(alpha-methylbenzyl)-3-(2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentyl)-4-[N-(R)-(alpha-methylbenzyl)imino]-2-azeti dineone (4a), a fully protected key intermediate (having the unnatural C-3 configuration) for the synthesis of known monobactam and bicyclic beta-lactam antibiotics, was synthesized in 91% yield with an ee of 91%. Application of chiral imines derived from acetaldehyde and propionaldehyde enable, depending on the solvent, the selective high yielding synthesis (de 60-99%; ee >95%) of any one of the four stereoisomers of 3-amino-4-alkyl-2-azetidinones, which are key intermediates for the synthesis of Aztreonam and related antibiotics. In Et2O, a weakly polar solvent, the trans isomers are formed, whereas the use of a polar THF/HMPA solvent mixture results in formation of the cis isomers. Reaction of the zinc enolate of 1c with the N-(4-methoxyphenyl)imine derivative 2i of (2R)-2,3-O-isopropylidene glyceraldehyde affords trans-(3R,4S)-3-amino-4-[(1'S)-1',2'-O-isopropylideneethyl]-2-azetidinone (10a) in excellent yield (de 86%; ee >98%), whereas reaction of the lithium enolate of 1c with the N-(trimethylsilyl)imine derivative 21 affords the cis-(3S,4S) isomer 10d (key intermediate for the synthesis of Carumonam) in good yield (de >90%; >90%). A rationale for the observed stereoselectivities in terms of highly ordered transition states is presented.

  DOI：

  10.1021/jo00040a034

文献信息

• Enantioselective synthesis of 3-amino-2-azetidinones via the ester enolate - imine condensation
  作者：Fred H. Van der Steen、Henk Kleijn、George J. P. Britovsek、Johann T. B. H. Jastrzebski、Gerard Van Koten

  DOI：10.1021/jo00040a034

  日期：1992.7

  Three approaches to the enantioselective synthesis of 3-amino-4-substituted-2-azetidinones by condensation of alpha-amino ester enolates with imines are described: (i) application of chiral ester derivatives of NN-diethylglycine; (ii) application of chiral N-(alpha-methylbenzyl)imines; and (iii) application of chiral imines derived from (2R)-2,3-O-isopropylideneglyceraldehyde. Zinc and aluminum enolates of (-)-menthyl- and (-)-bornyl NN-diethylglycine esters react with simple imines to selectively afford trans-3-(diethylamino)-2-azetidinones, but with a low chiral induction (ee 0-35%). However, reactions of the metal (Li, Zn, Al) ester enolates of (2,2,5,5-tetramethyl-1-aza-2,4-disilacyclopent-1-yl)acetic acid ethyl ester (1c) with N-(alpha-methylbenzyl)imines yield N-protected 3-amino-2-azetidinones in excellent yields and with very high diastereo- and enantioselectivities. The best results are obtained for the zinc-mediated reactions. For example, trans-(3R,4S)-1(R)-(alpha-methylbenzyl)-3-(2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentyl)-4-[N-(R)-(alpha-methylbenzyl)imino]-2-azeti dineone (4a), a fully protected key intermediate (having the unnatural C-3 configuration) for the synthesis of known monobactam and bicyclic beta-lactam antibiotics, was synthesized in 91% yield with an ee of 91%. Application of chiral imines derived from acetaldehyde and propionaldehyde enable, depending on the solvent, the selective high yielding synthesis (de 60-99%; ee >95%) of any one of the four stereoisomers of 3-amino-4-alkyl-2-azetidinones, which are key intermediates for the synthesis of Aztreonam and related antibiotics. In Et2O, a weakly polar solvent, the trans isomers are formed, whereas the use of a polar THF/HMPA solvent mixture results in formation of the cis isomers. Reaction of the zinc enolate of 1c with the N-(4-methoxyphenyl)imine derivative 2i of (2R)-2,3-O-isopropylidene glyceraldehyde affords trans-(3R,4S)-3-amino-4-[(1'S)-1',2'-O-isopropylideneethyl]-2-azetidinone (10a) in excellent yield (de 86%; ee >98%), whereas reaction of the lithium enolate of 1c with the N-(trimethylsilyl)imine derivative 21 affords the cis-(3S,4S) isomer 10d (key intermediate for the synthesis of Carumonam) in good yield (de >90%; >90%). A rationale for the observed stereoselectivities in terms of highly ordered transition states is presented.