(1-benzyl-4-benzylcarbamoyl-2-oxo-butyl)-carbamic acid benzyl ester | 521305-71-5

• 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: (1-benzyl-4-benzylcarbamoyl-2-oxo-butyl)-carbamic acid benzyl ester
• 英文别名: (5S)-N-benzyl 5-benzyloxycarbonylamino-4-oxo-6-phenylhexanamide；benzyl N-[(2S)-6-(benzylamino)-3,6-dioxo-1-phenylhexan-2-yl]carbamate
• CAS: 521305-71-5
• 化学式: C₂₇H₂₈N₂O₄
• 分子量: 444.53
• InChiKey: HKJKRLHDZAPFSC-DEOSSOPVSA-N

物化性质

• 沸点：
  699.7±55.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1-benzyl-4-benzylcarbamoyl-2-oxo-butyl)-carbamic acid benzyl ester 在 (S)-alpine-hydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以71%的产率得到(4S,5S)-N-benzyl-5-benzyloxycarbonylamino-6-phenyl-4-hydroxy-hexane amide
  参考文献：
  名称：

  Further studies in the acyl-type radical additions promoted by SmI 2 : mechanistic implications and stereoselective reduction of the keto-functionality

  摘要：

  Attempts were made to promote the carbonyl coupling of cyclohexanone to 4-pyridylthioesters of N-carbamate-protected amino acids with the one electron reducing agent, samarium diiodide. Such reactions proved unsuccessful due to the inability of the ketyl-type radical anion intermediate to be reduced to the corresponding dianion at -78degreesC. Nevertheless, these results explain our recently published work on the high efficiency of the SmI2-mediated acyl-type radical additions of the same thioesters with electron deficient alkenes [J. Am. Chem. Soc. 2003, 125, 4030]. A study was also undertaken to examine methods for the stereoselective reduction of N-carbamate-protected amino ketones to either the syn- or anti-vicinal amino alcohols. In most cases, LiAl(0-t-Bu)(3)H and (S)-Alpine-Hydride were found to effectively provide the anti- and syn-amino alcohols, respectively. The SmI2-promoted reduction of the same ketones afforded a majority of the syn-isomer with selectivities of approximately 5:1. However, in one case, the SmI2-promoted reduction was found to be more effective than that of (S)-Alpine-Hydride. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.07.016
• 作为产物：
  描述：

  N-苄基丙烯酰胺 、 Cbz-phenylalanine 4-pyridylthioester 在 samarium diiodide 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以66%的产率得到(1-benzyl-4-benzylcarbamoyl-2-oxo-butyl)-carbamic acid benzyl ester
  参考文献：
  名称：

  SmI₂ Reduced Thioesters as Synthons of Unstable Acyl Radicals:  Direct Synthesis of Potential Protease Inhibitors via Intermolecular Radical Addition

  摘要：

  Aromatic alpha-heterosubstituted thioesters were found to undergo radical 1,4-addition reactions to a series of alpha,beta-unsaturated amides and one ester when subjected to the single electron reducing agent, samarium diiodide, at -78 degrees C. These thioesters derived from alpha-amino acids represent a synthetically useful synthon of unstable acyl radicals. This reaction conveniently provides access to gamma-ketoamides and esters in yields up to 90%, structures that are common in various protease inhibitors derived from peptides. Examples with acryloyl and methacryloyl derivatives of alpha-amino acids and dipeptides lead directly to tri- and tetrapeptide mimetics possessing the gamma-ketoamide functionality. No epimerization was observed with the mild conditions used for these reactions.

  DOI：

  10.1021/ja029662+

文献信息

• Can Decarbonylation of Acyl Radicals Be Overcome in Radical Addition Reactions? En Route to a Solution Employing <i>N</i>-Acyl Oxazolidinones and SmI₂/H₂O
  作者：Christina M. Jensen、Karl B. Lindsay、Rolf H. Taaning、Jakob Karaffa、Anna Mette Hansen、Troels Skrydstrup

  DOI：10.1021/ja050420u

  日期：2005.5.1

  The application of acyl radicals in radical addition reactions in the absence of a CO atmosphere is generally limited to aryl or alpha-unsubstituted alkyl acyl radicals due to competing decarbonylations where the rate constant for this degradation process surpasses 104 s-1. In this work, a potential solution to avoid the problem of decarbonylations is presented employing N-acyl oxazolidinones which

  由于竞争性脱羰，在没有 CO 气氛的自由基加成反应中，酰基自由基的应用通常仅限于芳基或 α-未取代的烷基酰基自由基，其中该降解过程的速率常数超过 104 s-1。在这项工作中，提出了一种避免脱羰问题的潜在解决方案，使用 N-酰基恶唑烷酮，在二碘化钐和水的存在下将其还原为酰基自由基等价物。在丙烯酰胺、丙烯酸酯或丙烯腈的帮助下，正式酰基自由基加成的产物的产率高达 87%。给出了脱羰速率常数甚至超过 108 s-1 的例子。建议该反应通过类酮基中间体进行。
• Further studies in the acyl-type radical additions promoted by SmI 2 : mechanistic implications and stereoselective reduction of the keto-functionality
  作者：Lise M Mikkelsen、Christina M Jensen、Bettina Høj、Peter Blakskjær、Troels Skrydstrup

  DOI：10.1016/j.tet.2003.07.016

  日期：2003.12

  Attempts were made to promote the carbonyl coupling of cyclohexanone to 4-pyridylthioesters of N-carbamate-protected amino acids with the one electron reducing agent, samarium diiodide. Such reactions proved unsuccessful due to the inability of the ketyl-type radical anion intermediate to be reduced to the corresponding dianion at -78degreesC. Nevertheless, these results explain our recently published work on the high efficiency of the SmI2-mediated acyl-type radical additions of the same thioesters with electron deficient alkenes [J. Am. Chem. Soc. 2003, 125, 4030]. A study was also undertaken to examine methods for the stereoselective reduction of N-carbamate-protected amino ketones to either the syn- or anti-vicinal amino alcohols. In most cases, LiAl(0-t-Bu)(3)H and (S)-Alpine-Hydride were found to effectively provide the anti- and syn-amino alcohols, respectively. The SmI2-promoted reduction of the same ketones afforded a majority of the syn-isomer with selectivities of approximately 5:1. However, in one case, the SmI2-promoted reduction was found to be more effective than that of (S)-Alpine-Hydride. (C) 2003 Elsevier Ltd. All rights reserved.
• SmI₂ Reduced Thioesters as Synthons of Unstable Acyl Radicals:  Direct Synthesis of Potential Protease Inhibitors via Intermolecular Radical Addition
  作者：Peter Blakskjær、Bettina Høj、Ditte Riber、Troels Skrydstrup

  DOI：10.1021/ja029662+

  日期：2003.4.1

  Aromatic alpha-heterosubstituted thioesters were found to undergo radical 1,4-addition reactions to a series of alpha,beta-unsaturated amides and one ester when subjected to the single electron reducing agent, samarium diiodide, at -78 degrees C. These thioesters derived from alpha-amino acids represent a synthetically useful synthon of unstable acyl radicals. This reaction conveniently provides access to gamma-ketoamides and esters in yields up to 90%, structures that are common in various protease inhibitors derived from peptides. Examples with acryloyl and methacryloyl derivatives of alpha-amino acids and dipeptides lead directly to tri- and tetrapeptide mimetics possessing the gamma-ketoamide functionality. No epimerization was observed with the mild conditions used for these reactions.