ethyl (+/-)-trans-2-oxo-1,4-diphenyl-azetidine-3-carboxylate

• 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: ethyl (+/-)-trans-2-oxo-1,4-diphenyl-azetidine-3-carboxylate
• 英文别名: Ethyl 1,4-diphenyl-2-oxaazetidine-3-carboxylate；trans-3-ethoxycarbonyl-1,4-diphenyl-azetidin-2-one；ethyl trans-1,4-diphenylazetidin-2-one-3-carboxylate；(3RS,4SR)-ethyl-2-oxo-1,4-diphenylazetidine-3-carboxylate；ethyl (3R,4S)-2-oxo-1,4-diphenylazetidine-3-carboxylate
• 化学式: C₁₈H₁₇NO₃
• 分子量: 295.338
• InChiKey: RHOLVWBTPQMIQW-HZPDHXFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (+/-)-trans-2-oxo-1,4-diphenyl-azetidine-3-carboxylate 在 pig liver esterase 、 三乙胺 作用下， 以 水 为溶剂， 生成 1,4-二苯基-2-氮杂环丁酮
  参考文献：
  名称：

  Differential effects of stereochemistry and C-4 substituents on the enantioselectivity of PLE and PPL catalyzed hydrolysis of 3,4-disubstituted β-lactams

  摘要：

  Pig Liver Esterase (PLE) and Pig Pancreas Lipase (PPL) catalysed hydrolysis of (+/-)trans-3-carbethoxy and (+/-) cis-3-acetoxymethyl 4-substituted beta-lactams revealed interesting dependence on C-3, C-4 stereochemistry and nature of C-4 substituents. (C) 1997, Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(96)02381-7
• 作为产物：
  描述：

  N-Benzyl-2-diazo-N-phenylmalonamic acid ethyl ester 在 dirhodium tetraacetate 作用下， 以 二氯甲烷 为溶剂， 反应 144.0h， 以61%的产率得到ethyl (+/-)-trans-2-oxo-1,4-diphenyl-azetidine-3-carboxylate
  参考文献：
  名称：

  Ligand Effects in the Rhodium(II)-Catalyzed Reactions of .alpha.-Diazoamides. Oxindole Formation is Promoted by the Use of Rhodium(II) Perfluorocarboxamide Catalysts

  摘要：

  An improved procedure for the preparation of ethyl 2-diazomalonyl chloride ws developed which involves the reaction of ethyl diazoacetate with triphosgene. Using this diazo acid chloride, it was possible to prepare a variety of diazoamides from substituted amines. The rhodium(II)-catalyzed decomposition of these diazoamides was studied in order to probe the chemoselectivity of the carbenoid intermediates in intramolecular insertion reactions. Rhodium(II) acetate decomposition of N-benzyl-2-diazo-N-phenylmalonamic acid ethyl ester resulted in intramolecular C-H insertion to give ethyl 1,4-diphenyl-2-oxoazetidine-3-carboxylate. By changing the catalyst ligand to trifluoroacetamide, beta-lactam formation was completely suppressed in favor of the aromatic C-H insertion which produces an oxindole as the only detectable product. The competition between aliphatic and aromatic carbon-hydrogen insertion of 2-diazo-N-phenylmalonamic acid ethyl ester provides another example of ligand effectiveness in controlling chemoselectivity in dirhodium(II)-catalyzed metal carbene reactions. Thus, treatment of the N-isobutyldiazoanilide with rhodium(II) acetate results in exclusive aliphatic C-H insertion giving 4,4-dimethyl-2-oxo-1-phenylpyrrolidine-3-carboxylic acid ethyl ester, while the perfluorobutyramide ligand promotes oxidinole formation by aromatic C-H insertion. Several other rhodium(II)-catalyzed reactions were studied and were found to be highly catalyst dependent, rhodium(II) perfluorocarboxamides promoting aromatic C-H insertion, and hence oxindole formation, over O-H insertion, cyclization onto adjacent triple bonds, or cyclization to generate 1,3-dipolar intermediates.

  DOI：

  10.1021/jo00088a028

文献信息

• Stereoselective control in the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents: experimental investigation and theoretical rationalization
  作者：Hengzhen Qi、Xinyao Li、Jiaxi Xu

  DOI：10.1039/c0ob00783h

  日期：——

  The stereoselectivity of the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents was investigated experimentally by determination of the product stereochemistry and theoretically via DFT calculations. The results indicate that imines preferentially attack the less sterically hindered exo-side of the ketenes to generate zwitterionic intermediates. Subsequently, for cyclic imines, the intermediates undergo a conrotatory ring closure directly to produce β-lactams, while for linear imines, the imine moiety of the intermediates isomerizes to more stable intermediates, which further undergo a conrotatory ring closure to afford trans-β-lactams. The steric hindrance and the isomerization, rather than the torquoelectronic effect, play crucial roles in controlling the stereoselectivity in the practical Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents, although the unaccessible borylketene with a powerful electron acceptor group controls the stereoselectivity torquoelectronically, in theory.

  通过确定产物立体化学和基于密度泛函理论（DFT）的计算，实验上研究了涉及带有电子受体取代基的单取代乙烯酮的斯陶丁格反应的立体选择性。结果表明，亚胺优先攻击乙烯酮上立体障碍较小的外侧，生成内鎓离子中间体。随后，对于环状亚胺，中间体直接进行协同环合反应生成β-内酰胺；而对于线性亚胺，中间体的亚胺部分异构化为更稳定的中间体，后者进一步进行协同环合反应，产生反式β-内酰胺。在实际涉及带有电子受体取代基的单取代乙烯酮的斯陶丁格反应中，立体障碍和异构化而不是扭曲电子效应在控制立体选择性中起着关键作用，尽管在理论上，具有强电子受体基团的不可获得的硼乙烯酮通过扭曲电子效应控制立体选择性。
• Mechanistic Investigation of the Ring Opening in the Staudinger Cycloaddition Involving Ketenes with Electron-Withdrawing Substituents
  作者：Shanyan Mo、Jiaxi Xu

  DOI：10.1002/hlca.201100483

  日期：2012.7

  The cycloaddition of ketenes and imines (Staudinger cycloaddition) is a general method for the synthesis of various β‐lactams. However, reactions of imines and ketenes with electron‐withdrawing substituents produce α,β‐unsaturated alkenamides, ring‐opening products of the intermediates generated from imines and the ketenes, even as sole products, besides the desired β‐lactams. The mechanism of the

  烯酮和亚胺的环加成（Staudinger环加成）是合成各种β-内酰胺的通用方法。然而，亚胺和乙烯酮与吸电子取代基的反应会产生α，β-不饱和烯酰胺，由亚胺和乙烯酮生成的中间体的开环产物，甚至是唯一的产物，除了所需的β-内酰胺。研究了α，β-不饱和烯酰胺的形成机理。结果表明，α，β-不饱和烯酰胺是通过碱诱导的CC键异构化，然后形成的氮杂环丁烯（= 1,2-二氢氮杂环丁烷;参见方案3）进行电环开环。
• Base-switched annuloselectivity in the reactions of ethyl malonyl chloride and imines
  作者：Zhanhui Yang、Siqi Li、Zhong Zhang、Jiaxi Xu

  DOI：10.1039/c4ob01454e

  日期：——

  and [2 + 2 + 2] selectivity, in the reactions of ethyl malonyl chloride and imines is successfully realized. In the presence of the weak nucleophilic base 2-chloropyridine, the reactions deliver ethyl trans-β-lactam-3-carboxylates as the exclusive [2 + 2] products in up to 93% yields, while with the strong nucleophilic N-methylimidazole as the base, the reactions give rise to 2,3-dihydro-1,3-oxazin-4-one

  在乙基丙二酰氯与亚胺的反应中，成功实现了碱基转换的环选择性，即[2 + 2]和[2 + 2 + 2]选择性。在弱亲核碱2-氯吡啶存在下，反应以最高[93％]的产率提供反式-β-内酰胺-3-羧酸乙酯作为独家[2 + 2]产物，而强亲核N-甲基咪唑在此基础上，通过涉及一个分子的分子的正式[2 + 2 + 2]环加成反应，以唯一的产物形式生成2,3-二氢-1,3-恶嗪-4-酮衍生物，唯一产率高达99％。亚胺和由丙二酰氯生成的两个烯酮分子。值得注意的是，乙基反式-β-内酰胺-3-羧酸酯是第一次直接由乙基丙二酰氯与亚胺的反应合成。机理讨论表明，环选择性是由有机碱的亲核性控制的。
• A Versatile Method for the Synthesis of 3-Alkoxycarbonyl <i>β</i>-Lactam Derivatives
  作者：Lei Jiao、Qianfeng Zhang、Yong Liang、Shiwei Zhang、Jiaxi Xu

  DOI：10.1021/jo052135z

  日期：2006.1.1

  various imines and subsequent desulfurization reactions were employed to synthesize 3-ethoxycarbonyl β-lactam derivatives. The results indicate that the current approach provides a convenient, mild, and versatile method for synthesizing a variety of 3-alkoxycarbonyl trans-β-lactam derivatives with good to excellent yields and diastereoselectivities.

  乙氧基羰基（苯硫基）乙烯酮与各种亚胺的酮-亚胺环加成反应（Staudinger反应）和随后的脱硫反应被用于合成3-乙氧基羰基β-内酰胺衍生物。结果表明，目前的方法提供用于合成各种3-烷氧羰基的一个方便的，轻度，和通用的方法反式- β内酰胺衍生物具有良好至优异的产率和非对映选择性。
• Enantioselective synthesis of β-lactams via the IndaBox–Cu(II)-catalyzed Kinugasa reaction
  作者：Takao Saito、Tomohiro Kikuchi、Hiroaki Tanabe、Junichi Yahiro、Takashi Otani

  DOI：10.1016/j.tetlet.2009.06.050

  日期：2009.9

  The enantioselective Kinugasa reaction of nitrones with terminal alkynes in the presence of 20 mol % of IndaBox–Cu(OTf)2 and di-sec-butylamine (1.5 equiv) produced β-lactams with the highest level of enantiomeric excesses among the catalytic enantioselective Kinugasa reactions reported so far.

  在20 mol％IndaBox–Cu（OTf）2和二仲丁胺（1.5当量）的存在下，硝酮与末端炔烃的对映选择性Kinugasa反应生成的β-内酰胺在催化对映选择性Kinugasa中具有最高的对映体过量水平迄今已报道了反应。