cis-1-(p-methoxyphenyl)-3-isopriopyl-4-formyl-2-azetidinone | 133505-01-8

• 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: cis-1-(p-methoxyphenyl)-3-isopriopyl-4-formyl-2-azetidinone
• 英文别名: cis-4-Formyl-3-isopropyl-1-(4-methoxyphenyl)azetidin-2-one；(2S,3S)-1-(4-methoxyphenyl)-4-oxo-3-propan-2-ylazetidine-2-carbaldehyde
• CAS: 133505-01-8
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: WLCRDWBYVVOKED-OLZOCXBDSA-N

物化性质

• 沸点：
  459.7±40.0 °C(Predicted)
• 密度：
  1.203±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 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-methoxyphenyl)-3-isopriopyl-4-formyl-2-azetidinone 在 Jones'reagent 作用下， 以 丙酮 为溶剂， 反应 4.0h， 以90%的产率得到cis-3-isopropyl-1-(4-methoxyphenyl)-4-oxoazetidine-2-carboxylic acid
  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
• 作为产物：
  描述：

  异戊酰氯 在 盐酸 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 1.5h， 生成 cis-1-(p-methoxyphenyl)-3-isopriopyl-4-formyl-2-azetidinone
  参考文献：
  名称：

  A novel, general, totally stereoselective one-pot synthesis of cis-3-substituted 4-formylazetidin-2-ones

  摘要：

  A general, totally stereoselective one-pot synthesis of cis-3-substituted-4-formylazetidin-2-ones based upon the reaction of acid chlorides and 1,4-bis-(4-methoxyphenyl)-1,4-diazabuta-1,3-diene, as synthetic equivalent of the corresponding unknown alpha-formylimine, has been developed.

  DOI：

  10.1016/s0040-4039(00)74892-1

文献信息

• Base-Promoted Isomerization of <i>cis</i>-4-Formyl-2-azetidinones:  Chemoselective <i>C</i>4-Epimerization vs Rearrangement to Cyclic Enaminones
  作者：Benito Alcaide、Moustafa F. Aly、Carolina Rodríguez、Alberto Rodríguez-Vicente

  DOI：10.1021/jo991984h

  日期：2000.6.1

  N-(p-methoxyphenyl)-beta-lactams can be used, and (ii) transformation is less compatible with heteroatomic substituents bonded to the C3 position of the 2-azetidinone ring. A highly general solution to these problems relies on the use of sodium carbonate as the isomerization reagent in different solvents. We also describe a novel base-promoted rearrangement of the beta-lactam ring to cyclic enaminones 6

  描述了两种简单，有效和互补的方法，用于顺式-4-甲酰基-2-氮杂环丁烷酮1-3的区域特异性C4表异构化。第一种方法是在苄基三丁基溴化铵（3-4 mol％）作为相转移催化剂的情况下，在室温下于苯的非均相介质中使用40％的二甲胺水溶液作为试剂。该转化耐受2-氮杂环丁酮环的C 3上的烷基，烯基，炔基，芳基和烷氧基取代基。然而，这种异构化的局限性如下：（i）仅可使用N-（对甲氧基苯基）-β-内酰胺，并且（ii）转化与键合于2-氮杂环丁酮C3位的杂原子取代基的相容性较低。环。对于这些问题的高度通用的解决方案取决于在不同溶剂中使用碳酸钠作为异构化试剂。
• The unusual Baeyer-Villiger rearrangement of β-lactam aldehydes: Totally stereoselective entry to cis-3-substituted 4-formyloxy-2-azetidinones
  作者：Benito Alcaide、Moustafa F. Aly、Miguel A. Sierra

  DOI：10.1016/0040-4039(95)00492-u

  日期：1995.5

  Baeyer-Villiger oxidation of 4-formyl-β-lactams 1 with m-chloroperbenzoic acid in dichloromethane at room temperature is shown to be a convenient method for the preparation of 4-formyloxy-β-lactams 2. Some reactions of novel compounds 2 are also desrcribed.

  的拜尔-维利格氧化4-甲酰基- β内酰胺1与米中在室温下的二氯甲烷氯过苯甲酸被证明是4-甲酰-β内酰胺的制备的简便方法2。还描述了新型化合物2的一些反应。
• Ring Expansion versus Cyclization in 4-Oxoazetidine-2- carbaldehydes Catalyzed by Molecular Iodine: Experimental and Theoretical Study in Concert
  作者：Benito Alcaide、Pedro Almendros、Gema Cabrero、Ricardo Callejo、M. Pilar Ruiz、Manuel Arnó、Luis R. Domingo

  DOI：10.1002/adsc.201000171

  日期：——

  yield and high diastereoselectivity, through a C3C4 bond cleavage of the β‐lactam nucleus. Interestingly, in contrast to the iodine‐catalyzed reactions of 3‐alkoxy‐β‐lactam aldehydes which lead to the corresponding γ‐lactam derivatives (rearrangement adducts), the reactions of 3‐aryloxy‐β‐lactam aldehydes under similar conditions gave β‐lactam‐fused chromanes (cyclization adducts) as the sole products

  在叔丁基二甲基甲硅烷基氰化物或烯丙基和炔丙基三甲基硅烷的存在下，分子碘（10摩尔％）可有效催化4-氧杂氮杂环丁烷-2-甲醛的扩环，从而提供受保护的5-官能化-3,4-二羟基吡咯烷酮-2-酮具有良好的收益率和高非对映选择性，通过C3 β-内酰胺核的C4键裂解。有趣的是，与3-烷氧基-β-内酰胺醛的碘催化反应生成相应的γ-内酰胺衍生物（重排加合物）相反，在相似条件下3-芳氧基-β-内酰胺醛的反应得到了β-内酰胺。内酰胺稠合的苯并二氢吡喃（环化加合物）是唯一的产品，通过涉及C3芳环和甲醛的独家亲电芳族取代。为了支持机械方案，已经进行了理论研究。
• Efficient Entry to Highly Functionalized β-Lactams by Regio- and Stereoselective 1,3-Dipolar Cycloaddition Reaction of 2-Azetidinone-Tethered Nitrones. Synthetic Applications
  作者：Benito Alcaide、Pedro Almendros、Jose M. Alonso、Moustafa F. Aly、Carmen Pardo、Elena Sáez、M. Rosario Torres

  DOI：10.1021/jo025924e

  日期：2002.10.1

  Racemic as well as optically pure 2-azetidinone-tethered nitrones, both cyclic and acyclic, were smoothly prepared from 4-oxoazetidine-2-carbaldehydes. The regio- and diastereoselectivities of the intermolecular 1,3-dipolar cycloaddition reactions of 2-azetidinone-tethered nitrones with substituted alkenes and alkynes were investigated. 2-Azetidinone-tethered nitrones on reacting with various dipolarophiles yielded isoxazolinyl-, isoxazolidinyl-, or fused polycyclic-beta-lactams, exhibiting good regio- and facial stereoselectivity in the most of the cases. In addition, some interesting transformations of these cycloadducts were performed, yielding aziridinyl beta-lactams or functionalized beta-alkoxycarbonyl gamma-lactams (derivatives of the aza analogue of paraconic acid).
• C4,C4‘-Bis-β-lactam to Fused Bis-γ-lactam Rearrangement
  作者：Benito Alcaide、Yolanda Martín-Cantalejo、Javier Pérez-Castells、Miguel A. Sierra、Angeles Monge

  DOI：10.1021/jo960826c

  日期：1996.1.1

  Optically pure cis,cis-C4,C4'-bis-beta-lactams 1a-d are obtained in good to excellent yields, in a single step, following two different approaches. Staudinger reaction of (S)-(4-phenyl-2-oxooxazolidinyl)acetyl chloride (2a) and p-anisyldiimine gave the corresponding bis-beta-lactam la as a single enantiomer. The reaction of glyoxal diimine derived from (S)-alpha-phenylethylamine and different alkoxy-substituted acid chlorides gave diastereomeric mixtures of cis,cis-bis-beta-lactams 1b-d, enantiomers at the bicyclic skeleton. The configuration of all compounds has been determined by X-ray diffraction analysis of enantiomerically pure aldehyde 4a and bis-beta-lactam Ib-a. The remaining bicyclic lactams have been chemically correlated to compound 1b-alpha and their configurations assigned. Starting from enantiomerically pure 4-formyl-2-azetidinone 4b, sequential imine formation and ketene cycloaddition allowed the synthesis of differently substituted, optically pure cis,cis-C4,C4'-bis-beta-lactams If-i in good overall yields. C4,C4'-Bis-beta-lactams smoothly rearranged to fused trans,trans-bis-gamma-lactams 7 upon basic treatment (NaOMe/MeOH) in a totally stereoselective process. The presence of alkyl groups attached to the lactam nitrogen inhibits the rearrangement. Differently substituted (aryl and alkyl substituents in either rings) bicyclic p-lactam systems gave the selective opening of the ring with the aromatic substituent attached to the lactam nitrogen. Monocyclic 2-azetidinones 8 with an amino ester side chain at C4 are then obtained. The synthesis of trans,cis-C4,C4'-bis-beta-lactam Ij and trans,trans-C4,C4'-bis-beta-lactam 11 has also been effected in the racemic form. Compound Ij with a trans,cis stereochemistry rearranged to cis,trans-bis-gamma-lactam 7d in the presence of base while the trans,trans-bicycle 11 gave monocyclic 2-azetidinone 8c with an amino ester side chain. Finally, trans,trans-bis-gamma-lactam 11 can be synthesized in a single step from glyoxal diimine 3a employing an excess of lithium isovalerate. A reaction pathway to account for all the observed data is proposed.