(4-nitrophenyl)methyl (2S,5R)-3,7-dioxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4-nitrophenyl)methyl (2S,5R)-3,7-dioxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate
• 化学式: C₁₃H₁₀N₂O₇
• 分子量: 306.232
• InChiKey: MGTJMEHRHAOJDO-MNOVXSKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  119
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4-nitrophenyl)methyl (2S,5R)-3,7-dioxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate 在 双氧水 作用下， 以 乙腈 为溶剂， 生成 4-Nitrobenzyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate
  参考文献：
  名称：

  β-Lactam-Based Azomethine Ylide Reactivity. Expedient Synthesis of Carbapenams and Carbapenems

  摘要：

  DOI：

  10.1021/ja9637560
• 作为产物：
  描述：

  (2S,5S)-3-[2-Hydroxy-eth-(Z)-ylidene]-7-oxo-4-oxa-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid 4-nitro-benzyl ester 在 臭氧 作用下， 生成 (4-nitrophenyl)methyl (2S,5R)-3,7-dioxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate
  参考文献：
  名称：

  β-Lactam-Based Azomethine Ylide Reactivity. Expedient Synthesis of Carbapenams and Carbapenems

  摘要：

  DOI：

  10.1021/ja9637560

文献信息

• The azomethine ylide strategy for β-lactam synthesis. Azapenams and 1-azacephams
  作者：David Brown、Giles A. Brown、Mark Andrews、Jonathan M. Large、Dominique Urban、Craig P. Butts、Neil J. Hales、Timothy Gallagher

  DOI：10.1039/b203890k

  日期：——

  Reaction of the β-lactam-based oxazolidinone 5 with N-sulfonylimines provides the exo and endo azapenams 8 in 22–54% yield. The reactivity of 2H-azirines as 1,3-dipolarophiles towards β-lactam-based azomethine ylides derived from oxazolidinones 5 and 15 has also been evaluated. Azirines 11 and 12a provide cycloadducts 13a,b and 16 respectively, which incorporate the novel 2,6-diazatricyclo[4.2.0.02,4]octan-7-one ring system. These adducts were resistant towards C–N cleavage as the basis of an entry to 1-azacephams (1,5-diazabicyclo[4.2.0]octan-8-ones) 4. The use of the 3-(4-methoxyphenyl)-2H-azirine 19 provides a labile initial cycloadduct, which undergoes in situ ring-cleavage and further reaction to give the 2 ∶ 1 adduct 1-azacepham 22. The initial product is stable when 3-(4-nitrophenyl)-2H-azirine 23 is employed, and cycloadducts 24a and 24b are converted under mild reducing conditions to the 1-azacepham derivatives 25 and 26.

  β-内酰胺基恶唑啉酮5与N-磺酰亚胺反应生成外环和内环氮杂佩兰8，产率为22-54%。还评估了2H-氮杂环丙烷作为1,3-偶极亲偶极体与源自恶唑啉酮5和15的β-内酰胺基亚胺叶立德的反应活性。氮杂环丙烷11和12a分别生成含新型2,6-二氮杂三环[4.2.0.02,4]辛烷-7-酮环系的环加成物13a,b和16。这些加成物对C-N键断裂具有抗性，从而为获得1-氮杂头孢烷（1,5-二氮杂双环[4.2.0]辛烷-8-酮）4提供了途径。使用3-(4-甲氧苯基)-2H-氮杂环丙烷19得到了一个不稳定的初始环加成物，它通过原位环断裂和进一步反应生成2∶1加成物1-氮杂头孢烷22。当使用3-(4-硝基苯基)-2H-氮杂环丙烷23时，初始产物是稳定的，并且环加成物24a和24b在温和还原条件下转化为1-氮杂头孢烷衍生物25和26。
• Aldehydes and ketones as dipolarophiles: application to the synthesis of oxapenams
  作者：Mark D. Andrews、Giles A. Brown、Jonathan P. H. Charmant、Torren M. Peakman、Arlene Rebello、Kenneth E. Walsh、Timothy Gallagher、Neil J. Hales

  DOI：10.1039/a808688e

  日期：——

  2-Substituted (6a–e) and 2, 2-disubstituted oxapenams (6f–g) are obtained in one step by thermolysis of the β-lactam-based oxazolidinone 4 in the presence of aldehydes and reactive ketones respectively; the C(6)-substituted oxazolidinone variant 7 reacts with hexafluoroacetone to give the enantiomerically pure oxapenam 8.

  通过热分解β-内酰胺基噁唑烷酮4，在醛和反应性酮的存在下，分别一步获得2-取代的噁帕南（6a–e）和2,2-双取代的噁帕南（6f–g）；C(6)-取代的噁唑烷酮变体7与六氟醋酮反应，生成对映体纯的噁帕南8。
• The azomethine ylide strategy for β-lactam synthesis. A comprehensive mechanistic evaluation
  作者：David Brown、Giles A. Brown、Sarah R. Martel、Denis Planchenault、Evelyn Turmes、Kenneth E. Walsh、Richard Wisedale、Neil J. Hales、Colin W. G. Fishwick、Timothy Gallagher

  DOI：10.1039/b010046n

  日期：——

  The release of azomethine ylide reactivity from oxazolidinones such as 4a/4b and 7 is proposed to involve a stepwise fragmentation via12 and 13 followed by cycloaddition (to an alkene) leading to adduct 14, which then undergoes decarboxylation under the reaction conditions to give the observed product 15. In the case of CC-based dipolarophiles, the cycloaddition is concerted and stereospecific, and the cycloaddition step is rate determining. Extensive experimental, together with computational data, including racemisation and kinetic studies, as well as the changes in reactivity associated with varying key structural features associated with the β-lactam based oxazolidinones is presented in support of the favoured mechanistic postulate. The fragmentation–cycloaddition–decarboxylation sequence is an alternative pathway for the release of an azomethine ylide from an oxazolidinone to that process already well established for N-alkyl oxazolidinones (concerted decarboxylation before cycloaddition). The N-acyl component associated with 4 may influence this change in mechanism, but specific structural features associated with the β-lactam system (ring strain and the presence of a malonyl moiety) are most likely responsible for the mechanistic divergence that is observed.

  从恶唑烷酮（例如 4a/4b 和 7）中释放偶氮甲碱叶立德反应活性涉及通过 12 和 13 进行逐步裂解，然后进行环加成（与烯烃），得到加合物 14，然后在反应条件下进行脱羧，得到观察到的产物15。对于基于CC的亲偶极试剂，环加成是协同的和立体特异性的，并且环加成步骤是速率决定的。广泛的实验以及计算数据，包括外消旋和动力学研究，以及与β-内酰胺基恶唑烷酮相关的不同关键结构特征相关的反应性变化，都提出来支持所青睐的机械假设。断裂→环加成→脱羧顺序是从恶唑烷酮中释放偶氮甲碱叶立德的另一种途径，该途径已经为N-烷基恶唑烷酮建立了良好的过程（环加成之前的协同脱羧）。与 4 相关的 N-酰基成分可能会影响这种机制的变化，但与 β-内酰胺系统相关的特定结构特征（环应变和丙二酰基部分的存在）最有可能导致观察到的机械分歧。
• Trapping highly reactive dipolarophiles. Exploiting the mechanism associated with the azomethine ylide strategy for β-lactam synthesis
  作者：Giles A. Brown、Kirsty M. Anderson、Jonathan M. Large、Denis Planchenault、Dominique Urban、Neil J. Hales、Timothy Gallagher

  DOI：10.1039/b103271m

  日期：——

  Highly reactive thioaldehydes 7, which are generated transiently by thermolysis of thiosulfinates 6, are trapped using azomethine ylide (derived from the β-lactam based oxazolidinone 1) to give 2-substituted penams 8. Diethyl thioxomalonate 10 and the selenoxo analogue 13, both of which are generated transiently via a retro Diels–Alder reaction, undergo 1,3-dipolar cycloaddition reactions with 1 to

  高反应性 硫代醛 7，它们是由热分解硫代亚磺酸盐6，被捕集甲亚胺叶立德 （源自基于β-内酰胺的 恶唑烷酮 1）产生2-取代便士 8。硫代己二酸二乙酯10和硒代氧类似物13都是通过逆Diels-Alder反应瞬时产生的，它们经过1，3-偶极环加成反应后生成1，得到同分异构体。佩纳姆 分别为11a和异戊烷11b，以及2，2-二取代硒代庚烷14。
• A Direct and Convergent Approach to Penams and Penems
  作者：Denis Planchenault、Richard Wisedale、Timothy Gallagher、Neil J. Hales

  DOI：10.1021/jo962367l

  日期：1997.5.1