[3-Phenyl-indan-(1E)-ylidene]-acetic acid ethyl ester | 71823-70-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: [3-Phenyl-indan-(1E)-ylidene]-acetic acid ethyl ester
• 英文别名: ethyl (2E)-2-(3-phenyl-2,3-dihydroinden-1-ylidene)acetate
• CAS: 71823-70-6
• 化学式: C₁₉H₁₈O₂
• 分子量: 278.351
• InChiKey: WWGNTMDWYOSGNP-FYWRMAATSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [3-Phenyl-indan-(1E)-ylidene]-acetic acid ethyl ester 在 4-碘甲苯 、 Olah′s reagent 、 triethylamine tris(hydrogen fluoride) 、 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 以52 %的产率得到ethyl 2,2-difluoro-4-phenyl-1,2,3,4-tetrahydronaphthalene-1-carboxylate
  参考文献：
  名称：

  Catalytic Ring Expanding Difluorination: An Enantioselective Platform to Access β,β‐Difluorinated Carbocycles

  摘要：

  Cyclic β,β‐difluoro‐carbonyl compounds have a venerable history as drug discovery leads, but limitations in the synthesis arsenal continue to impede chemical space exploration. This challenge is particularly acute in the arena of fluorinated medium rings where installing the difluoromethylene unit subtly alters the ring conformation by expanding the internal angle (∠C−CF2−C>∠C−CH2−C): this provides a handle to modulate physicochemistry (e.g. pKa). To reconcile this disparity, a highly modular ring expansion has been devised that leverages simple α,β‐unsaturated esters and amides, and processes them to one‐carbon homologated rings with concomitant geminal difluorination (6 to 10 membered rings, up to 95 % yield). This process is a rare example of the formal difluorination of an internal alkene and is enabled by sequential I(III)‐enabled O‐activation. Validation of enantioselective catalysis in the generation of unprecedented medium ring scaffolds is reported (up to 93 : 7 e.r.) together with X‐ray structural analyses and product derivatization.

  DOI：

  10.1002/anie.202403957
• 作为产物：
  描述：

  磷酰基乙酸三乙酯 、 3-苯基-1-茚酮 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 以4 %的产率得到[3-Phenyl-indan-(1E)-ylidene]-acetic acid ethyl ester
  参考文献：
  名称：

  Catalytic Ring Expanding Difluorination: An Enantioselective Platform to Access β,β‐Difluorinated Carbocycles

  摘要：

  Cyclic β,β‐difluoro‐carbonyl compounds have a venerable history as drug discovery leads, but limitations in the synthesis arsenal continue to impede chemical space exploration. This challenge is particularly acute in the arena of fluorinated medium rings where installing the difluoromethylene unit subtly alters the ring conformation by expanding the internal angle (∠C−CF2−C>∠C−CH2−C): this provides a handle to modulate physicochemistry (e.g. pKa). To reconcile this disparity, a highly modular ring expansion has been devised that leverages simple α,β‐unsaturated esters and amides, and processes them to one‐carbon homologated rings with concomitant geminal difluorination (6 to 10 membered rings, up to 95 % yield). This process is a rare example of the formal difluorination of an internal alkene and is enabled by sequential I(III)‐enabled O‐activation. Validation of enantioselective catalysis in the generation of unprecedented medium ring scaffolds is reported (up to 93 : 7 e.r.) together with X‐ray structural analyses and product derivatization.

  DOI：

  10.1002/anie.202403957

文献信息

• SMITH C. E.; WILLIAMSON W. R. N.; CASHIN C. H.; KITCHEN E. A., J. MED. CHEM., 1979, 22, NO 12, 1464-1469
  作者：SMITH C. E.、 WILLIAMSON W. R. N.、 CASHIN C. H.、 KITCHEN E. A.

  DOI：——

  日期：——