cis-1-(p-anisyl)-4-(formyl)-3-isopropylidene-2-azetidinone | 143902-60-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: cis-1-(p-anisyl)-4-(formyl)-3-isopropylidene-2-azetidinone
• 英文别名: cis-1-p-anisyl-4-formyl-3-isopropylideneazetidin-2-one；1-(4-Methoxyphenyl)-4-oxo-3-propan-2-ylideneazetidine-2-carbaldehyde
• CAS: 143902-60-7
• 化学式: C₁₄H₁₅NO₃
• 分子量: 245.278
• InChiKey: SUFCYGVORGASMK-UHFFFAOYSA-N

物化性质

• 沸点：
  384.9±42.0 °C(predicted)
• 密度：
  1.256±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 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：

  cis-1-(p-anisyl)-4-(formyl)-3-isopropylidene-2-azetidinone 在 chlorohydroalane 、 对甲苯磺酸 作用下， 以 乙醚 为溶剂， 生成 (2S,3R)-2-[1,3]Dioxan-2-yl-1-(4-methoxy-phenyl)-3-methyl-azetidine
  参考文献：
  名称：

  Novel Diethylaluminum Chloride Promoted Reactions of the Azetidine Ring:  Efficient and Stereocontrolled Entry to Functionalized Olefins, Pyrrolidines, and Pyrroles

  摘要：

  The first examples of Lewis acid promoted fragmentation or rearrangement of the azetidine ring are reported. Azetidine precursors, cis-beta-lactams, were easily available as single cis-diastereoisomers by the Staudinger reaction. Both cis- and trans-4-formyl-beta-lactams react with the appropriate dial or dithiol under acid catalysis to yield dioxolanes or dithiolanes, while reaction with trimethyl orthoformate or benzenethiol gave 4-acetal or thioacetal beta-lactams, respectively. Azetidines were smoothly obtained by reduction of easily available beta-lactams with monochloroalane (AlH2Cl), generated in situ from LiAlH4/AlCl3. The chemical reactivity of azetidines with AlEt2Cl was further investigated. Different substituted azetidines showed varied behavior on product formation during diethylaluminum chloride promoted reactions. Azetidines having 4-methoxyphenyl or 2-furyl groups at C2 and a benzyl or allyl substituent at nitrogen efficiently reacted with AlEt2Cl to give olefins stereoselectively through a fragmentation process, while acetal or thioacetal azetidines under the standard reaction conditions afforded in a stereocontrolled manner pyrrolidines as the sole product. Furthermore, thioacetal azetidines bearing a substituent at C3 on the azetidine ring that can promote aromatization (phenoxy or exocyclic double bond) gave pyrroles by reaction with AlEt2Cl.

  DOI：

  10.1021/jo991203c
• 作为产物：
  描述：

  1,4-bis(4'-methoxyphenyl)-1,4-diazabuta-1,3-diene 在 盐酸 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 苯 为溶剂， 反应 7.5h， 生成 cis-1-(p-anisyl)-4-(formyl)-3-isopropylidene-2-azetidinone
  参考文献：
  名称：

  Stereoselective preparation of mono- and bis-.beta.-lactams by the 1,4-diaza-1,3-diene - acid chloride condensation: scope and synthetic applications

  摘要：

  The dehydrochlorination of a variety of acid chlorides with triethylamine in the presence of 1,4-diaza 1,3-dienes gives in fair to excellent yields, with total stereoselectivity, cis-4-imino beta-lactams 2, cis-4-formyl beta-lactams 3, or C4,C4'-bis-beta-lactams 4, depending on the reaction conditions. The reaction tolerates a wide variety of substituents, including alkoxy, thiophenoxy, amino, aryl, alkyl, alkylidene, and halogen groups, at the ketene moiety. The synthetic versatility of compounds 3 has been demonstrated by their conversion to intermediates in the synthesis of carbapenems PS-5 and PS-6. Base-induced isomerization of compounds 4 to novel bis-gamma-lactams 5, which in turn are aza analogs of glycaric acids, occurred with total retention of the configuration. This process is formally the elongation of glyoxal in four carbons bearing four contiguous stereocenters with total stereoselectivity in only three or four synthetic steps.

  DOI：

  10.1021/jo00048a027

文献信息

• Accessing Skeletal Diversity under Iron Catalysis using Substrate Control: Formation of Pyrroles versus Lactones
  作者：Benito Alcaide、Pedro Almendros、M. Teresa Quirós

  DOI：10.1002/adsc.201100049

  日期：2011.3.7

  Worthy of note, in contrast to the iron‐catalyzed reactions of β‐lactam allenols which lead to γ‐lactones, the reaction of β‐lactam alkynols under identical conditions gives pyrroles. The gold‐catalyzed 6‐endo aminocyclization of these allenic γ‐lactones formed fused dihydropyridines. The iron‐catalyzed formation of pyrroles may proceed through a Meyer–Schuster rearrangement followed by β‐lactam ring opening

  由丙烯腈β-内酰胺醛制备的2-氮杂环丁酮系链的炔醇和烯丙醇用作氯化铁（III）催化发散扩环反应的起始原料。值得注意的是，与β-内酰胺烯醇的铁催化反应会生成γ-内酯相反，β-内酰胺醇在相同条件下的反应会生成吡咯。这些烯丙基γ-内酯的金催化6-内氨基氨基环化形成了稠合的二氢吡啶。吡咯的铁催化形成可通过迈耶-舒斯特重排进行，然后通过氨基攻击酮使β-内酰胺开环和环化。
• Stereoselective Synthesis of 3-Substituted 4-(Formyloxy)-2-azetidinones by the Unusual Baeyer−Villiger Reaction of β-Lactam Aldehydes. Scope and Synthetic Applications
  作者：Benito Alcaide、Moustafa F. Aly、Miguel A. Sierra

  DOI：10.1021/jo9612685

  日期：1996.1.1

  The Baeyer-Villiger oxidation of 4-formyl-beta-lactams 1 with m-CPBA gave 4-(formyloxy) beta-lactams 2 in a simple, efficient, and totally stereoselective process. This reaction is one of the scarce examples of the preferred migration of a carbon moiety in an aliphatic aldehyde. The influence of the substituents at N1 and C3 of the four-membered ring in the Baeyer-Villiger rearrangement has been studied. Thus, alkyl, alkenyl, aryl, and alkyloxy 3-substituted-1-(p-anisyl)-2-azetidinone 1 form exclusively 4-(formyloxy) beta-lactams 2. Amide or acetoxy substituents at C3 of the four-membered ring produce mixtures of 4-(formyloxy) beta-lactams 2 and 4-carboxy beta-lactams 5. The exclusive formation of carboxy derivatives is observed sometimes for 1-alkyl-substituted-2-azetidinones 1. 4-(Formyloxy) beta-lactams 2 are suitable starting materials to prepare different 4-unsubstituted beta-lactams 9 using beta-hydroxy amides 8 as isolable intermediates. The overall transformation 4-formyl-2-azetidinone to 4-unsubstituted beta-lactam is an easy and convenient stereoselective route to these interesting types of compounds.
• Chemodivergence in Alkene/Allene Cycloetherification of Enallenols: Iron versus Noble Metal Catalysis
  作者：Benito Alcaide、Pedro Almendros、Teresa Martínez del Campo

  DOI：10.1002/chem.200801166

  日期：2008.9.8
• Novel Diethylaluminum Chloride Promoted Reactions of the Azetidine Ring:  Efficient and Stereocontrolled Entry to Functionalized Olefins, Pyrrolidines, and Pyrroles
  作者：Benito Alcaide、Pedro Almendros、Cristina Aragoncillo、Nati R. Salgado

  DOI：10.1021/jo991203c

  日期：1999.12.1

  The first examples of Lewis acid promoted fragmentation or rearrangement of the azetidine ring are reported. Azetidine precursors, cis-beta-lactams, were easily available as single cis-diastereoisomers by the Staudinger reaction. Both cis- and trans-4-formyl-beta-lactams react with the appropriate dial or dithiol under acid catalysis to yield dioxolanes or dithiolanes, while reaction with trimethyl orthoformate or benzenethiol gave 4-acetal or thioacetal beta-lactams, respectively. Azetidines were smoothly obtained by reduction of easily available beta-lactams with monochloroalane (AlH2Cl), generated in situ from LiAlH4/AlCl3. The chemical reactivity of azetidines with AlEt2Cl was further investigated. Different substituted azetidines showed varied behavior on product formation during diethylaluminum chloride promoted reactions. Azetidines having 4-methoxyphenyl or 2-furyl groups at C2 and a benzyl or allyl substituent at nitrogen efficiently reacted with AlEt2Cl to give olefins stereoselectively through a fragmentation process, while acetal or thioacetal azetidines under the standard reaction conditions afforded in a stereocontrolled manner pyrrolidines as the sole product. Furthermore, thioacetal azetidines bearing a substituent at C3 on the azetidine ring that can promote aromatization (phenoxy or exocyclic double bond) gave pyrroles by reaction with AlEt2Cl.
• Stereoselective preparation of mono- and bis-.beta.-lactams by the 1,4-diaza-1,3-diene - acid chloride condensation: scope and synthetic applications
  作者：Benito Alcaide、Yolanda Martin-Cantalejo、Javier Perez-Castells、Julian Rodriguez-Lopez、Miguel A. Sierra、Angeles Monge、Virginia Perez-Garcia

  DOI：10.1021/jo00048a027

  日期：1992.10

  The dehydrochlorination of a variety of acid chlorides with triethylamine in the presence of 1,4-diaza 1,3-dienes gives in fair to excellent yields, with total stereoselectivity, cis-4-imino beta-lactams 2, cis-4-formyl beta-lactams 3, or C4,C4'-bis-beta-lactams 4, depending on the reaction conditions. The reaction tolerates a wide variety of substituents, including alkoxy, thiophenoxy, amino, aryl, alkyl, alkylidene, and halogen groups, at the ketene moiety. The synthetic versatility of compounds 3 has been demonstrated by their conversion to intermediates in the synthesis of carbapenems PS-5 and PS-6. Base-induced isomerization of compounds 4 to novel bis-gamma-lactams 5, which in turn are aza analogs of glycaric acids, occurred with total retention of the configuration. This process is formally the elongation of glyoxal in four carbons bearing four contiguous stereocenters with total stereoselectivity in only three or four synthetic steps.