trans-1-(4-methoxyphenyl)-3-methyl-4-phenylazetidin-2-one

• 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: trans-1-(4-methoxyphenyl)-3-methyl-4-phenylazetidin-2-one
• 英文别名: (3R,4S)-1-(4-methoxyphenyl)-3-methyl-4-phenylazetidin-2-one
• 化学式: C₁₇H₁₇NO₂
• 分子量: 267.327
• InChiKey: WMKHTJRBFOWKJH-WBMJQRKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  trans-1-(4-methoxyphenyl)-3-methyl-4-phenylazetidin-2-one 在 ammonium cerium(IV) nitrate 作用下， 以75%的产率得到trans-3-Methyl-4-phenyl-azetidinon-(2)
  参考文献：
  名称：

  Optically Active Aminoalcohol Promoted Addition of 2-Pyridylthioester Boron Enolates to Imines: Enantioselective One-pot Synthesis of β-Lactams

  摘要：

  The enolates derived from 2-pyridylthioesters by treatment with BCl3 . Me(2)S and enantiomerically pure aminoalcohols react with aromatic and heteroaromatic imines to afford beta-lactams in a convenient one-pot procedure and in up to 78% e.e. The aminoalcohol can be employed both as the metal ligand and as the base to generate the enolate. Among several aminoalcohols tested, N-methylephedrine turned our to be the more efficient in terms of stereoselectivity.

  DOI：

  10.1016/0040-4020(95)00503-z
• 作为产物：
  描述：

  cis-2-<(4-methoxyphenyl)imino>-3-methyl-4-phenyloxethane 在 potassium tert-butylate 、 氢碘酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 trans-1-(4-methoxyphenyl)-3-methyl-4-phenylazetidin-2-one
  参考文献：
  名称：

  2-Iminooxetane Chemistry. 4. Synthesis of .beta.-Substituted Propionamides

  摘要：

  beta-substituted propionamides (RCHXCR(1)R(2)CONHAr) were synthesized in high yields by addition of protic and aprotic Lewis acids (C6H5SO3H, CF3COOH, CH3COOH, HI, MgBr2, ZnI2, CH3OH, H2O,2,4,6-(NO2)(3)C6H2OH) to 2-iminooxetanes. Studies on the stereochemistry of the acid addition to unsymmetrically C3,C4-monosubstituted 2-iminooxetanes indicate that product distribution depends on the steric and electronic nature of the substitutents of the oxetane moiety as well as on the nucleophilicity of the conjugate base derived from the acid.

  DOI：

  10.1021/jo00083a036

文献信息

• Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe
  作者：Motoyuki Isoda、Kazuyuki Sato、Yurika Kunugi、Satsuki Tokonishi、Atsushi Tarui、Masaaki Omote、Hideki Minami、Akira Ando

  DOI：10.3762/bjoc.12.157

  日期：——

  An effective synthesis for syn-β-lactams was achieved using a Rh-catalyzed reductive Mannich-type reaction. A rhodium–hydride complex (Rh–H) derived from diethylzinc (Et₂Zn) and a Rh catalyst was used for the 1,4-reduction of an α,β-unsaturated ester to give a Reformatsky-type reagent, which in turn, reacted with an imine to give the syn-β-lactam. Additionally, the reaction was applied to the synthesis of (±)-ezetimibe, a potent β-lactamic cholesterol absorption inhibitor.

  通过使用钌催化的还原曼尼希型反应，成功实现了对 syn-β-内酰胺的有效合成。从二乙基锌（Et₂Zn）和钌催化剂派生的钌-氢化物络合物（Rh–H）用于α,β-不饱和酯的1,4-还原，以提供类似改革试剂的反应物，后者再与亚胺反应生成 syn-β-内酰胺。此外，该反应还被应用于合成 (±)-依泽替米，这是一种强效的β-内酰胺胆固醇吸收抑制剂。

• Solvent-Free, One-Pot Synthesis of β-Lactams by the Sc(OTf)3-Catalyzed Reaction of Silyl Ketene Thiocetals with Imines
  作者：Maurizio Benaglia、Franco Cozzi、Alessandra Puglisi

  DOI：10.1002/ejoc.200601127

  日期：2007.6

  A solvent-free, catalytic, one-pot synthesis of β-lactams is described. The reaction involves the reaction between silyl ketene thioacetals derived from 2-pyridyl thioesters and imines at room temperature in the presence of catalytic amounts of Sc(OTf)3 and in the absence of solvent. Extension of this procedure to the synthesis of an enantiomerically pure azetidinone, a precursor of industrially relevant

  描述了 β-内酰胺的无溶剂、催化、一锅合成。该反应涉及衍生自 2-吡啶基硫酯的甲硅烷基乙烯酮硫缩醛与亚胺在室温下在催化量的 Sc(OTf) 3 存在下且不存在溶剂的反应。还报道了该程序扩展到合成对映异构纯氮杂环丁酮，工业相关生物活性 β-内酰胺的前体。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
• A general and versatile synthesis of 3-phenylthio β-lactams as lead molecules for 3-methyl-2-azetidinones
  作者：Seema Kanwar、S. D. Sharma

  DOI：10.1002/jhet.5570440523

  日期：2007.9

  Ketene-imine cycloaddition using phosphorus oxychloride and benzenesulfonyl chloride under the described reaction conditions yielded trans 3-phenylthio 2-azetidinones in good yields. Desulfurization using Raney nickel and alkylation finally afforded trans 3-methyl-2-azetidinones in a stereoselective manner.

  在所述反应条件下，使用三氯氧化磷和苯磺酰氯的乙胺-亚胺环加成反应以良好的收率得到反式3-苯硫基2-氮杂环丁烷酮。最后使用阮内镍进行脱硫和烷基化，以立体选择性方式得到反式3-甲基-2-氮杂环丁烷酮。
• Diastereoselective Synthesis of <i>syn</i>-β-Lactams Using Rh-Catalyzed Reductive Mannich-Type Reaction of α,β-Unsaturated Esters
  作者：Motoyuki Isoda、Kazuyuki Sato、Masato Funakoshi、Keiko Omura、Atsushi Tarui、Masaaki Omote、Akira Ando

  DOI：10.1021/acs.joc.5b01233

  日期：2015.8.21

  The combination of Et2Zn and RhCl(PPh3)3 led to the facile generation of a rhodium–hydride complex (Rh–H) that catalyzed the 1,4-reduction of α,β-unsaturated esters. The resulting rhodium enolate performed as a Reformatsky-type reagent and reacted with various imines to give syn-β-lactams in good to excellent yields with high diastereoselectivity.

  Et 2 Zn和RhCl（PPh 3）3的组合导致容易生成铑-氢化物络合物（Rh-H），该络合物催化α，β-不饱和酯的1,4-还原。所得的烯醇铑作为Reformatsky型试剂起作用，并与各种亚胺反应，以良好的非对映异构体收率以优异的产率得到合成的-β-内酰胺。
• Stereoselective one-pot synthesis of β-lactams by Lewis acid promoted condensation of silylketene thioacetals with imines
  作者：Rita Annunziata、Mauro Cinquini、Franco Cozzi、Valentina Molteni、Olaf Schupp

  DOI：10.1016/0040-4020(95)01083-1

  日期：1996.2

  A series of silylketene thioacetals derived from 2-pyridylthioesters have been prepared and the configuration of some of them has been determined by NMR spectroscopy. In the presence of Lewis acids these compounds stereoselectively react with imines to afford β-lactams in a convenient one-pot procedure. An enantioselective β-lactam synthesis promoted by a chiral Lewis acid is also described.

  制备了一系列衍生自2-吡啶基硫酯的甲硅烷基烯酮硫缩醛，其中一些的构型已通过NMR光谱测定。在路易斯酸的存在下，这些化合物与亚胺立体选择性地反应，以方便的一锅法制得β-内酰胺。还描述了由手性路易斯酸促进的对映选择性β-内酰胺合成。