(S)-N-ethylmethylidene-1-phenylethylamine | 37696-18-7

• 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)-N-ethylmethylidene-1-phenylethylamine
• 英文别名: N-propylidene-(S)-α-methylbenzylamine；N-[(1S)-1-phenylethyl]propan-1-imine
• CAS: 37696-18-7
• 化学式: C₁₁H₁₅N
• 分子量: 161.247
• InChiKey: UHVWRYGIKJCQIN-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  12.4
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (S)-N-ethylmethylidene-1-phenylethylamine 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
• 作为产物：
  描述：

  (S)-(-)- α-甲基苄胺 、 丙醛 在 magnesium sulfate 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-N-ethylmethylidene-1-phenylethylamine
  参考文献：
  名称：

  非对映选择性地将高阶铜酸盐和锌铜试剂添加到衍生自（S）-1-苯乙胺的亚胺中

  摘要：

  考察了向（S）-1-苯基乙胺衍生的脂族和芳族手性亚胺的非对映选择性地添加了高阶（HO）铜酸盐和锌铜试剂。脂族的手性亚胺与（烯丙基）反应2 CuCNLi 2和（正丁基）2的Cu（CN）栗2在BF的存在3 ·的Et 2 O和我3的SiCl在高diastereoselection，而CC 6 ħ 11的Cu（CN ZnI和烯丙基Cu（CN）ZnBr可以在不添加添加剂的情况下以相当的收率得到手性胺。此外，据报道合成了针对δ-氨基酸的关键中间体。

  DOI：

  10.1016/s0040-4020(99)00418-4

文献信息

• Asymmetric syntheses of amino acids by addition of cyanide to the schiff bases in the presence of cyanide-modified hemin-copolymer
  作者：Kiyoshi Saito、Kaoru Harada

  DOI：10.1016/s0040-4039(01)80738-3

  日期：1989.1

  Sterically controlled addition reactions of CN group to the Schiff bases by using CN-modified hemin-copolymer were carried out, and the optical yields (80–95 e.e.) of the resulting amino acids were much higher than that obtained without hemin-copolymer.

  使用CN修饰的血红素共聚物进行了CN基团与Schiff碱的立体控制加成反应，所得氨基酸的旋光产率（80-95 ee）比不含血红素共聚物的光学产率高得多。
• Asymmetric synthesis of β-lactams. I. The reaction of dimethylketene silyl acetal with (S)-alkylidene(1-arylethyl)amines promoted by titanium tetrachloride
  作者：Iwao Ojima、Shin-ichi Inaba

  DOI：10.1016/s0040-4039(00)71491-2

  日期：1980.1

  Asymmetric synthesis of β-lactams by means of the reaction of dimethylketene silyl acetal with (S)-alkylidene(1-arylethyl)amines in the presence of titanium tetrachloride was studied. The extent of the asymmetric induction was in the range of 44–78% (diastereomeric purity 72–89%) and the (S)-configuration was turned to be preferentially induced at the 4C position of the resulting β-lactams.

  研究了在四氯化钛存在下，二甲基乙烯酮甲硅烷基乙缩醛与（S）-亚烷基（1-芳基乙基）胺的反应，不对称合成β-内酰胺。不对称诱导的程度为44-78％（非对映异构体纯度为72-89％），（S）-构型被优先诱导在所得β-内酰胺的4 C位置。
• Diastereoselective addition of higher order cuprates and zinc-copper reagents to imines derived from (S)-1-phenylethylamine
  作者：Marco Bandini、Pier Giorgio Cozzi、Achille Umani-Ronchi、Marzia Villa

  DOI：10.1016/s0040-4020(99)00418-4

  日期：1999.6

  The diastereoselective addition of higher order (H.O.) cuprates and zinc-copper reagents to aliphatic and aromatic chiral imines derived from (S)-1-phenylethylamine was examined. Aliphatic chiral imines react with (Allyl)2CuCNLi2 and (n-Bu)2Cu(CN)Li2 in the presence of BF3·Et2O and Me3SiCl in high diastereoselection, while c-C6H11Cu(CN)ZnI and AllylCu(CN)ZnBr afford chiral amines in comparable yields

  考察了向（S）-1-苯基乙胺衍生的脂族和芳族手性亚胺的非对映选择性地添加了高阶（HO）铜酸盐和锌铜试剂。脂族的手性亚胺与（烯丙基）反应2 CuCNLi 2和（正丁基）2的Cu（CN）栗2在BF的存在3 ·的Et 2 O和我3的SiCl在高diastereoselection，而CC 6 ħ 11的Cu（CN ZnI和烯丙基Cu（CN）ZnBr可以在不添加添加剂的情况下以相当的收率得到手性胺。此外，据报道合成了针对δ-氨基酸的关键中间体。
• 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.