(4S)-3,3-difluoro-4-phenylazetidin-2-one | 252681-07-5

• 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: (4S)-3,3-difluoro-4-phenylazetidin-2-one
• 英文别名: (S)-3,3-difluoro-4-phenylazetidin-2-one
• CAS: 252681-07-5
• 化学式: C₉H₇F₂NO
• 分子量: 183.157
• InChiKey: RWHMRWLTDWSYQS-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R)-3-氨基丁酸叔丁酯 、 (4S)-3,3-difluoro-4-phenylazetidin-2-one 在 Burkholderia cepacia lipase 作用下， 以 异丙醚 为溶剂， 反应 15.0h， 以96%的产率得到tert-butyl (3R)-3-[[(3S)-3-amino-2,2-difluoro-3-phenylpropanoyl]amino]butanoate
  参考文献：
  名称：

  Burkholderia cepacia lipase and activated β-lactams in β-dipeptide and β-amino amide synthesis

  摘要：

  The work describes fluorine-activated and N-Boc-activated beta-lactams as acyl donors to N-nucleophiles in the presence of Burkholderia cepacia lipase (lipase PS-D). Fluorine activation at the beta-lactam ring causes the ring to open in high enantioselectivity and allows the preparation of beta-dipeptides and beta-amino amides. in the case of N-Boc-activation, the chemical ring opening is significant. beta-Dipeptide formation can then be considerably enhanced by the presence of lipase PS-D and/or by temperature. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2008.07.017
• 作为产物：
  描述：

  benzaldehyde N-boc imine 在 (S)-3,3'-bis(9-anthracenyl)-6,6'-dimethyl-1,1'-biphenyl-2,2'-phosphate 、 异丙基氯化镁 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 六氟异丙醇 为溶剂， 反应 70.0h， 生成 (4S)-3,3-difluoro-4-phenylazetidin-2-one
  参考文献：
  名称：

  Chiral Phosphoric Acid Catalyzed Enantioselective Synthesis of β-Amino-α,α-difluoro Carbonyl Compounds

  摘要：

  A biphenol-based chiral phosphoric acid bearing a 9-anthryl group at each of the 3,3'-positions catalyzed the asymmetric Mannich-type reaction of N-Boc Imine with difluoroenol silyl ethers In the presence of MS3A In THF to afford beta-amino-alpha,alpha-difluoroketones In good yields and with excellent enantioselectivities. Optically pure 3,3-difluoroazetidin-2-one was readily synthesized from the Mannich-adduct.

  DOI：

  10.1021/ol200374m

文献信息

• Regio- and Stereoselective Lipase-Catalysed Acylation of Methyl α-<scp>D</scp>-Glycopyranosides with Fluorinated β-Lactams
  作者：Riku Sundell、Elina Siirola、Liisa T. Kanerva

  DOI：10.1002/ejoc.201402800

  日期：2014.10

  Burkholderia cepacia lipase (lipase PS-D) catalysed acylation with 3,3-difluoro-4-phenyl-, -thiophen-3-yl- and -4-pyridylazetidin-2-ones was examined for the formation of N-Boc-protected 6-O-acylated sugar–β-amino acid conjugates from methyl α-D-galacto-, -gluco- and mannopyranosides and Boc2O. The 6-O-acylated glycopyranoside–β-amino acid conjugates were isolated and characterized. The low solubility

  洋葱伯克霍尔德氏菌脂肪酶（脂肪酶 PS-D）用 3,3-二氟-4-苯基-、-噻吩-3-基-和-4-吡啶基氮杂环丁烷-2-酮催化酰化，研究了 N-Boc 保护的形成来自甲基 α-D-半乳糖-、-葡萄糖-和吡喃甘露糖苷以及 Boc2O 的 6-O-酰化糖-β-氨基酸缀合物。分离并表征了 6-O-酰化吡喃糖苷-β-氨基酸偶联物。葡糖苷和吡喃甘露糖苷的低溶解度以及吡啶基氮杂环丁酮的高反应性限制了产物的形成。通过氟取代基的存在激活 β-内酰胺环被证明是酶促酰化反应所必需的。外消旋β-内酰胺底物的(S)-对映异构体与糖反应。
• Enantioselective acylation of alcohols with fluorinated β-phenyl-β-lactams in the presence of Burkholderia cepacia lipase
  作者：Xiang-Guo Li、Maria Lähitie、Mari Päiviö、Liisa T. Kanerva

  DOI：10.1016/j.tetasy.2007.06.033

  日期：2007.7

  the acylation of alcohols with 3,3-difluoro-4-phenylazetidin-2-one rac-1, trans-3-fluoro-4-phenylazetidin-2-one rac-2 and 4-phenylazetidin-2-one rac-3 in the presence of immobilized lipase PS from Burkholderia cepacia in dry tert-butyl methyl ether (TBME). Fluorine activation in the compounds studied was essential in order to split the β-lactam ring with lipase PS. The highly enantioselective ring

  本文着重研究醇与3,3-二氟-4-苯基氮杂环丁烷-2-one rac - 1，反式-3-氟-4-苯基氮杂环丁烷-2-one rac - 2和4-苯基氮杂环丁烷2的酰化作用。-酮的外消旋- 3中存在固定的脂肪酶PS从洋葱伯克霍尔德氏菌的无水叔丁基甲基醚（TBME）。为了用脂肪酶PS裂解β-内酰胺环，所研究化合物中的氟活化是必不可少的。rac - 1和rac - 2的高对映选择性开环用甲醇（还研究了1-丁醇）可以制备（R /（3 R，4 R））-β-内酰胺类未反应的对映体和（S /（2 S，3 S））-β-氨基酯为对映体，ee≥99％。在相同条件下，rac - 3完全不起作用。还讨论了酶制剂中水引起竞争性水解的可能性。
• Rhodium-catalyzed Reformatsky-type reaction for asymmetric synthesis of difluoro-β-lactams using menthyl group as a chiral auxiliary
  作者：Atsushi Tarui、Daiki Ozaki、Naoko Nakajima、Yuto Yokota、Yasser S. Sokeirik、Kazuyuki Sato、Masaaki Omote、Itsumaro Kumadaki、Akira Ando

  DOI：10.1016/j.tetlet.2008.04.101

  日期：2008.6

  developed a new methodology for the asymmetric Reformatsky-type reaction of (−)-menthyl bromodifluoroacetate (2) with imine in the presence of RhCl(PPh3)3. Ester 2 with the cost-effective chiral auxiliary gave (S)-difluoro-β-lactams in moderate to good yields and high diastereoselectivities through spontaneous removal of the auxiliary.

  我们开发了一种新的方法，用于在RhCl（PPh 3）3存在下（-）-薄荷基溴二氟乙酸酯（2）与亚胺的不对称Reformatsky型反应。带有成本有效的手性助剂的酯2通过自发除去助剂，以中等至良好的收率和较高的非对映选择性获得（S）-二氟-β-内酰胺。
• Chemoenzymatic preparation of fluorine-substituted β-lactam enantiomers exploiting Burkholderia cepacia lipase
  作者：Xiang-Guo Li、Liisa T. Kanerva

  DOI：10.1016/j.tetasy.2007.10.003

  日期：2007.10

  Both enantiomers of fluorinated and non-fluorinated 4-phenyl-2-azetidinones are prepared in high enantiopurities (ee 99%) by a chemoenzymatic method, using a double resolution technique to N-hydroxymethylated beta-lactams in the presence of Burkholderia cepacia lipase as the source of enantiopurity. N-Deprotections yield the beta-lactam enantiomers from the corresponding hydroxymethylated counterparts using KMnO4 in a mixture of acetone and water. (c) 2007 Elsevier Ltd. All rights reserved.
• Enantioselective Synthesis of α,α-Difluoro-β-amino Acid and 3,3-Difluoroazetidin-2-one via the Reformatsky-Type Reaction of Ethyl Bromodifluoroacetate with Chiral 1,3-Oxazolidines
  作者：Stéphane Marcotte、Xavier Pannecoucke、Christian Feasson、Jean-Charles Quirion

  DOI：10.1021/jo990868b

  日期：1999.11.1

  Chiral oxazolidines 2a-e can be diastereoselectively alkylated with BrCF2CO2Et to furnish 3,3-difluoroazetidin-2-ones 3a-e with up to 99% de. Selective cleavage of the chiral appendage provided the corresponding unsubstituted azetidinones. Formation of optically pure a,a-difluoro-P-amino acids 5a-c can be achieved by acidic hydrolysis of N-vinyl-azetidin-2-ones.