(R)-3-(4-fluorobenzyl)-2-piperidone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (R)-3-(4-fluorobenzyl)-2-piperidone
• 英文别名: (R)-3-(p-fluorobenzyl)piperidone；(S)-3-p-flurorobenzyl-2-piperidone；(3R)-3-[(4-fluorophenyl)methyl]piperidin-2-one
• 化学式: C₁₂H₁₄FNO
• 分子量: 207.248
• InChiKey: YZHUFKNGGSTLGQ-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-3-(4-fluorobenzyl)-2-piperidone 在 lithium aluminium tetrahydride 作用下， 反应 12.0h， 生成 (R)-3-(4-fluorobenzyl)piperidine
  参考文献：
  名称：

  铑催化的环外α，β-不饱和羰基化合物的不对称氢化。

  摘要：

  已开发出由Rh /双膦-硫脲（ZhaoPhos）催化的对环外α，β-不饱和羰基化合物的高度对映选择性氢化，可提供相应的α-手性环状内酯，内酰胺和酮，产率高且对映选择性极好（高达99％收率和99％ee）。显着地，底物和催化剂之间的氢键在该转变中起关键作用。该协议的合成用途已通过有效合成手性3-（4-氟苄基）哌啶（一种生物活性分子的关键手性片段）得到了证明。

  DOI：

  10.1039/c9ob02536g
• 作为产物：
  描述：

  哌啶酮 在 [(S,S)-(BDPP)Ir(COD)]BF₄ 、 potassium tert-butylate 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 20.0~55.0 ℃ 、448.17 kPa 条件下， 反应 25.5h， 生成 (R)-3-(4-fluorobenzyl)-2-piperidone
  参考文献：
  名称：

  Enantioselective Hydrogenation of 3-Alkylidenelactams:  High-Throughput Screening Provides a Surprising Solution

  摘要：

  High-throughput screening of 256 potential catalysts (8 metal precursors x 32 phosphine ligands) has identified [(BDPP)Ir(COD)]BF4 as a catalyst for the enantioselective hydrogenation of 3-alkylidenelactams. This result is surprising given the highly flexible backbone of the BDPP ligand and the ineffectiveness of this catalyst in other applications. The asymmetric hydrogenation appears fairly general for five- and six-membered lactams and in one case has been scaled up to a 20 kg level.

  DOI：

  10.1021/ja028043y

文献信息

• Process for the manufacture of optically active 3-substituted lactams by asymmetric hydrogenation of 3-alkylidenelactams
  申请人：——

  公开号：US20040010139A1

  公开（公告）日：2004-01-15

  The present invention relates generally to processes for the efficient production optically active 3-substituted lactams of formula (I) 1 process, comprising: contacting a compound of formula (II): 2 with hydrogen under a suitable pressure in the presence of an iridium complex of the formula (R 2 )IrL + X − wherein L is a chelating diene, X is a non coordinating anion, and R 2 is selected from 3

  本发明通常涉及一种高效生产光学活性的3-取代内酰胺的方法，其中包括：将式（II）的化合物与氢在适当压力下在(R2)IrL+X−的铱配合物存在下接触，其中L是螯合二烯，X是非配位阴离子，R2是选择自3。
• Stereoselective Process for a CCR3 Antagonist
  作者：Tai-Yuen Yue、Douglas D. McLeod、Kevin B. Albertson、Steven R. Beck、Joerg Deerberg、Joseph M. Fortunak、William A. Nugent、Lilian A. Radesca、Liya Tang、Cathie Dong Xiang

  DOI：10.1021/op050202l

  日期：2006.3.1

  A convergent, multikilogram, stereoselective synthesis of 1 is described. A key fragment, (S)-3-(4-fluorobenzyl)piperidine (2) was synthesized from valerolactam in three steps using our recently discovered Ir-BDPP-catalyzed asymmetric hydrogenation. Another key fragment, (IR,2R)-2-(benzyloxycarbonylamino)cyclohexanecarboxaldehyde (3) was synthesized from meso-hexahydrophthalic anhydride in seven steps. The stereochemistry was set in the first step of this sequence via a quinidine-mediated desymmetrization of the meso-anhydride. Coupling of the fragments 2 and 3 followed by deprotection provided the penultimate 23. The active pharmaceutical ingredient (API) free base I was obtained by treatment of 23 with the aminothiazole fragment 4 under mild conditions.
• Rhodium-catalyzed asymmetric hydrogenation of exocyclic α,β-unsaturated carbonyl compounds
  作者：Jiaxin Yang、Xiuxiu Li、Cai You、Shuailong Li、Yu-Qing Guan、Hui Lv、Xumu Zhang

  DOI：10.1039/c9ob02536g

  日期：——

  A highly enantioselective hydrogenation of exocyclic α,β-unsaturated carbonyl compounds catalyzed by Rh/bisphosphine-thiourea (ZhaoPhos) has been developed, giving the corresponding α-chiral cyclic lactones, lactams and ketones with high yields and excellent enantioselectivities (up to 99% yield and 99% ee). Remarkably, the hydrogen bond between the substrate and the catalyst plays a critical role

  已开发出由Rh /双膦-硫脲（ZhaoPhos）催化的对环外α，β-不饱和羰基化合物的高度对映选择性氢化，可提供相应的α-手性环状内酯，内酰胺和酮，产率高且对映选择性极好（高达99％收率和99％ee）。显着地，底物和催化剂之间的氢键在该转变中起关键作用。该协议的合成用途已通过有效合成手性3-（4-氟苄基）哌啶（一种生物活性分子的关键手性片段）得到了证明。
• Enantioselective Hydrogenation of 3-Alkylidenelactams:  High-Throughput Screening Provides a Surprising Solution
  作者：Tai-Yuen Yue、William A. Nugent

  DOI：10.1021/ja028043y

  日期：2002.11.1

  High-throughput screening of 256 potential catalysts (8 metal precursors x 32 phosphine ligands) has identified [(BDPP)Ir(COD)]BF4 as a catalyst for the enantioselective hydrogenation of 3-alkylidenelactams. This result is surprising given the highly flexible backbone of the BDPP ligand and the ineffectiveness of this catalyst in other applications. The asymmetric hydrogenation appears fairly general for five- and six-membered lactams and in one case has been scaled up to a 20 kg level.