(3R,4S)/(3S,4R)-1-benzyl-3-bromo-3-fluoro-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: (3R,4S)/(3S,4R)-1-benzyl-3-bromo-3-fluoro-4-phenylazetidin-2-one
• 英文别名: (3SR,4RS)-1-benzyl-3-bromo-3-fluoro-4-phenylazetidin-2-one；syn-1-benzyl-3-bromo-3-fluoro-4-phenylazetidin-2-one；1-benzyl-3-bromo-3-fluoro-4-phenylazetidin-2-one；(3S,4R)-1-benzyl-3-bromo-3-fluoro-4-phenylazetidin-2-one
• 化学式: C₁₆H₁₃BrFNO
• 分子量: 334.188
• InChiKey: GFMOGZXVFJWTRQ-GDBMZVCRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3R,4S)/(3S,4R)-1-benzyl-3-bromo-3-fluoro-4-phenylazetidin-2-one 在 正丁基锂 、 甲醇 作用下， 以 四氢呋喃 为溶剂， 反应 3.17h， 以76%的产率得到(3R,4S)/(3S,4R)-1-benzyl-3-fluoro-4-phenylazetidin-2-one
  参考文献：
  名称：

  Direct and Diastereoselective Alkylation and Aldol Reactions of α-Bromo-α-fluoro-β-lactams

  摘要：

  Herein, we describe the development of a method for the direct alkylation and aldol reaction of alpha-bromo-alpha-fluoro-beta-lactams. This method provides facile access to a wide range of 3-alkyl- and 3-hydroxyalkyl-fluoro-beta-lactams in good yields under mild conditions. The products were obtained with complete diastereoselectivity with regard to the relative configuration of the beta-lactam ring at C3 and C4 positions. The reaction conditions were tolerant of a broad range of electrophiles, which highlights the overall scope and utility of this procedure.

  DOI：

  10.1021/jo401072h
• 作为产物：
  描述：

  二溴氟乙酸乙酯 、 N-苄烯丁胺 在 diethylzinc 作用下， 以 乙醚 、 正己烷 为溶剂， 反应 1.0h， 以70%的产率得到(3R,4S)/(3S,4R)-1-benzyl-3-bromo-3-fluoro-4-phenylazetidin-2-one
  参考文献：
  名称：

  镍催化的仲α-溴-α-氟-β-内酰胺的α-芳基化：仲含氟亲电试剂的交叉偶联

  摘要：

  Ni /双（恶唑啉）催化α-溴-α-氟-β-内酰胺与多种芳基格氏试剂的高度非对映选择性交叉偶联反应，收率高达98％。非对映选择性地获得该产物作为反异构体。这是α-氟-β-内酰胺成功生产出多种α-芳基-α-氟-β-内酰胺的第一个成功的α-芳基化反应。

  DOI：

  10.1016/j.tet.2012.12.002

文献信息

• Simple, chemoselective, and diastereoselective Reformatsky-type synthesis of α-bromo-α-fluoro-β-lactams
  作者：Atsushi Tarui、Naoto Kawashima、Kazuyuki Sato、Masaaki Omote、Yoshihisa Miwa、Hideki Minami、Akira Ando

  DOI：10.1016/j.tetlet.2010.02.023

  日期：2010.4

  diastereoselective synthesis of syn-α-bromo-α-fluoro-β-lactams was achieved using the diethylzinc-mediated Reformatsky-type reaction of ethyl dibromofluoroacetate with imines. The reaction led to diastereomerically pure β-lactams in good to moderate yields (up to 78% yield) with only small amounts of aziridine derivatives. Noncyclized 3-amino-2-bromo-2-fluoro carboxylic esters, usual Reformatsky adducts, were

  使用二乙基氟代乙酸乙酯与亚胺的二乙基锌介导的Reformatsky型反应，可实现顺-α-溴-α-氟代-β-内酰胺的化学选择性和非对映选择性合成。该反应导致仅以少量的氮丙啶衍生物就可以以良好至中等的产率（高达78％的产率）得到非对映体纯的β-内酰胺。未形成非环化的3-氨基-2-溴-2-氟羧酸酯，通常为Reformatsky加合物。相反，在典型的Reformatsky条件下使用锌金属进行的反应的化学选择性较差，导致生成β-内酰胺和氮丙啶衍生物的混合物。
• Diastereoselective synthesis of 2-fluoroaziridine-2-carboxylates by Reformatsky-type aza-Darzens reaction
  作者：Atsushi Tarui、Naoto Kawashima、Kazuyuki Sato、Masaaki Omote、Akira Ando

  DOI：10.1016/j.tetlet.2010.06.030

  日期：2010.8

  The reaction of ethyl dibromofluoroacetate with imines using zinc metal gave 2-fluoroaziridine-2-carboxylates via aza-Darzens reaction of the primary product of the Reformatsky reaction with high diastereoselectivity in excellent yields (quantitative yield and Dr = 85:15). This chemoselective formation of 2-fluoroaziridines was achieved by using CH3CN as a solvent. Interestingly, the reaction proceeded

  使用锌金属使二溴氟乙酸乙酯与亚胺反应通过 Reformatsky 反应的主要产物的 aza-Darzens 反应得到 2-氟氮丙啶-2-羧酸盐，该反应具有高非对映选择性和优异的收率（定量收率和 Dr = 85:15）。这种 2-氟氮丙啶的化学选择性形成是通过使用 CH3CN 作为溶剂实现的。有趣的是，该反应在没有活化锌金属的情况下进行，这对于溴二氟乙酸盐的 Reformatsky 反应是必需的。没有形成α-溴-α-氟-β-内酰胺、四元环化产物和未环化的3-氨基-2-溴-2-氟羧酸酯，通常是Reformatsky加合物。
• Ligand-Promoted Asymmetric Imino-Reformatsky Reaction of Ethyl Dibromofluoroacetate
  作者：Atsushi Tarui、Haruka Nishimura、Takeshi Ikebata、Asuka Tahira、Kazuyuki Sato、Masaaki Omote、Hideki Minami、Yoshihisa Miwa、Akira Ando

  DOI：10.1021/ol500631j

  日期：2014.4.18

  An enantioselective Reformatsky reaction has been developed for the reaction of ethyl dibromofluoroacetate (1) with an imine. This method represents the first ligand-promoted imino-Reformatslcy approach to use a halofluoroacetate. The use of an amino alcohol ligand allowed for the preparation of enantioenriched alpha-bromo-alpha-fluoro-beta-lactams in good yields with enantioselectivities up to 96% ee. This process also provided access to beta-lactam rings bearing two stereogenic centers.
• Stereoselective Suzuki Coupling Reaction of an α-Bromo-α-fluoro-β-lactam
  作者：Akira Ando、Atsushi Tarui、Erina Miyata、Ayumi Tanaka、Kazuyuki Sato、Masaaki Omote

  DOI：10.1055/s-0034-1379637

  日期：——

  A new strategy has been developed for the synthesis of alpha-aryl-alpha-fluoro-beta-lactams via the Suzuki cross-coupling of alpha-bromo-alpha-fluoro-beta-lactam with a range of different aryl-(9-BBN) reagents. This method provides facile access to multisubstituted alpha-fluoro-beta-lactams in a diastereoselective manner. The synthetic utility of alpha-bromo-alpha-fluoro-beta-lactam has been demonstrated by the arylation of alpha-bromo-alpha-fluoro-beta-lactam.
• Ni-catalyzed α-arylation of secondary α-bromo-α-fluoro-β-lactam: cross-coupling of a secondary fluorine-containing electrophile
  作者：Atsushi Tarui、Shoji Kondo、Kazuyuki Sato、Masaaki Omote、Hideki Minami、Yoshihisa Miwa、Akira Ando

  DOI：10.1016/j.tet.2012.12.002

  日期：2013.2

  A highly diastereoselective cross-coupling reaction of an α-bromo-α-fluoro-β-lactam with a wide range of aryl Grignard reagents was catalyzed by Ni/bis(oxazoline) in yields of up to 98%. The product was obtained diastereoselectively as an anti-isomer. This is the first successful α-arylation of an α-fluoro-β-lactam to produce diverse α-aryl-α-fluoro-β-lactams.

  Ni /双（恶唑啉）催化α-溴-α-氟-β-内酰胺与多种芳基格氏试剂的高度非对映选择性交叉偶联反应，收率高达98％。非对映选择性地获得该产物作为反异构体。这是α-氟-β-内酰胺成功生产出多种α-芳基-α-氟-β-内酰胺的第一个成功的α-芳基化反应。