ethyl (2S,3S)-3-hydroxy-2-methyl-3-phenylpropanoate | 155320-73-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl (2S,3S)-3-hydroxy-2-methyl-3-phenylpropanoate
• 英文别名: ethyl (2S,3S)-3-hydroxy-2-methyl-3-phenylpropionate；Ethyl (2S,3S)-3-hydroxy-2-methyl-3-phenylpropionic acid；ethyl (2S,3S)-3-phenyl-3-hydroxy-2-methylpropionate；ethyl 3-hydroxy-2-methyl-3-phenylpropanoate
• CAS: 155320-73-3
• 化学式: C₁₂H₁₆O₃
• 分子量: 208.257
• InChiKey: DBYGIIOOKKCUKJ-ONGXEEELSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (2S,3S)-3-hydroxy-2-methyl-3-phenylpropanoate 在 三乙基硼 盐酸 、 三正丁基氢锡 、 phosphorus pentoxide 、 二异丁基氢化铝 、 magnesium 、 1,2-二溴乙烷 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 、 氯仿 、 水 、 甲苯 为溶剂， 反应 40.92h， 生成 ethyl (2R,3R,4R,5S)-3-hydroxy-2,4-dimethyl-5-methoxy-5-phenylpentanoate
  参考文献：
  名称：

  朝向的发散合成非对映选择性的自由基脱溴的方法合成-和反-丙酸酯单元，再加上对映选择性和/或对映选择性路易斯酸促进的羟醛缩合反应

  摘要：

  通过迭代对映和非对映选择性路易斯酸促进的醛醇缩合反应，然后进行非对映选择性自由基脱溴反应，已经开发出一种实用的方法学，该方法可用于合成聚酮化合物天然产物，可用于聚丙烯酸酯主链的对映选择性合成。由2-甲基-1,3-丙二醇衍生的外消旋醛与2-溴丙酸乙酯的甲硅烷基乙烯酮缩醛的手性草并氮杂硼硼烷酮促进的醛醇缩合反应导致相应的溴醛羟醛加合物的高度对映选择性形成，然后进行自由基脱溴与卜3 SNH在Et的存在3 B到发散给予顺式-和反-丙醛醇醛缩醛酸酯，是多用途的立体三联体。此外，还实现了丙酸酯单元的延长：手性顺式和反-α-甲基-β-保护的乙醛与甲硅烷基亲核试剂的BF 3 ·OEt 2促进的醛醇缩合反应以基本上完​​全的顺选择性进行。而TiCl 4促进的羟醛反应导致相当好的抗选择性。通过自由基还原将所得的溴代羟醛加合物发散地脱溴，得到完整的立体四线体。

  DOI：

  10.1016/j.tetasy.2003.06.005
• 作为产物：
  描述：

  ethyl (2S)-2-benzoylpropanate 在 吡啶硼烷 、 四氯化钛 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以91%的产率得到ethyl (2S,3S)-3-hydroxy-2-methyl-3-phenylpropanoate
  参考文献：
  名称：

  Chelation-controlled protocol for the diastereoselective reduction of ketones

  摘要：

  A new chelation-controlled, alpha-chiral ketone reduction protocol is presented based on titanium tetrachloride and a wide variety of reducing agents. Features of the proposed intermediate titanium chelates necessary to obtain high diastereoselectivity are discussed.

  DOI：

  10.1021/jo00083a004

文献信息

• A Divergent Synthesis of Essentially Enantiopure<i>syn</i>- and<i>anti</i>-Propionate Aldol Adducts Based on the Chiral 1,3,2-Oxazaborolidin-5-one-Promoted Asymmetric Aldol Reaction Followed by Diastereoselective Radical Reduction
  作者：Syun-ichi Kiyooka、Kazi Abuds Shahid

  DOI：10.1246/bcsj.74.1485

  日期：2001.8

  Essentially, enantiopure syn- and anti-propionate aldol adducts were divergently synthesized using a novel strategy which utilizes both the highly enantioselective 1,3,2-oxazaborolidin-5-one-promoted aldol reaction with a ketene silyl acetal derived from ethyl 2-bromo propionate and a highly diastereoselective radical debromination reaction. These procedures provide yields that increase to a level

  本质上，对映纯的合成和反丙醇醛加合物是使用一种新的策略不同地合成的，该策略利用高度对映选择性的 1,3,2-oxazaborolidin-5-one-促进的醛醇反应与衍生自乙基 2-溴的乙烯酮甲硅烷基缩醛丙酸盐和高度非对映选择性的自由基脱溴反应。这些程序提供的产率增加到可用于实际合成的水平。
• Synthesis of N-propionylated (S )-(−)-2-(pyrrolidin-2-yl)propan-2-ol and its use as a chiral auxiliary and selectivity marker in asymmetric aldol reactions
  作者：Erik Hedenström、Fredrik Andersson、Mats Hjalmarsson

  DOI：10.1039/b001730m

  日期：——

  The N-propionylated pyrrolidine derivative and chiral auxiliary, (S)-(−)-2-(pyrrolidin-2-yl)propan-2-ol, was synthesised and used in stereoselective aldol reactions with benzaldehyde. Differences in stereoselectivity were investigated as a function of temperature, solvent, chelating agent and the amount of the chelating agent used by monitoring the 1H NMR spectra of the aldol adducts that were obtained. Among the additives that were investigated, Cp2ZrCl2 induced higher anti-selectivity, while SnCl2 induced higher syn-selectivity respectively. TMSCl was found to induce high selectivity for one syn- and one anti-diastereomer. Varying the ligand sets on titanium additives was found to induce differences in selectivity, with (i-PrO)3TiCl exhibiting syn-selectivity and Cp2TiCl2 exhibiting anti-selectivity. Differences in reactivity and stereoselectivity were also found to depend upon the amount of Lewis acid that was added. Methods for removal of the auxiliary were also investigated. Acidic hydrolysis was used successfully to obtain the desired 3-hydroxy-2-methyl-3-phenylpropionic acids, but was found to give low yields and resulted in a large amount of epimerisation. Furthermore, the ethyl esters of these hydroxy acids are easy to separate into pure syn- and anti-diastereomers by LC.

  合成了N-丙酰化吡咯烷衍生物和手性辅助剂(S)-(β-)-2-(吡咯烷-2-基)丙醇-2，并在与苯甲醛的立体选择性醛醇反应中使用。通过监测获得的醛醇加合物的¹H NMR光谱，研究了立体选择性在温度、溶剂、螯合剂及使用的螯合剂量上的差异。研究的添加剂中，Cp₂ZrCl₂诱导了更高的反式选择性，而SnCl₂则诱导了更高的顺式选择性。发现TMSCl在高选择性上对一个顺式和一个反式二叠体具有影响。改变钛添加剂的配体组合被发现会导致选择性的差异，其中(i-PrO)₃TiCl表现出顺式选择性，而Cp₂TiCl₂则表现出反式选择性。反应性和立体选择性的差异也发现依赖于所添加的路易斯酸的量。还研究了去除辅助剂的方法。酸水解成功用于获得所需的3-羟基-2-甲基-3-苯基丙酸，但发现产率较低，并导致大量的异构化。此外，这些羟基酸的乙基酯可以通过液相色谱轻易分离为纯的顺式和反式二叠体。
• Enantio- and Diastereoselective Reductive Aldol Reactions with Iridium-Pybox Catalysts
  作者：Cun-Xiang Zhao、Matthew O. Duffey、Steven J. Taylor、James P. Morken

  DOI：10.1021/ol015859f

  日期：2001.6.1

  [see reaction]. A catalytic amount of [(cod)IrCl]2 and indane-pybox converts diethylmethylsilane, methyl acrylate, and certain aldehydes to the derived reductive aldol adduct with good enantio- and diastereocontrol.

  [请参阅反应]。催化量的[（cod）IrCl] 2和茚满-Pybox将二乙基甲基硅烷，丙烯酸甲酯和某些醛转化为衍生的具有良好对映异构和非对映异构控制的还原性醛醇加合物。
• Enantioselective Aldol Reaction Using Bornane-2,3-diol-Aluminum Complex as a Chiral Lewis Acid
  作者：Makoto Shimizu、Manabu Kawamoto、Yasushi Yamamoto、Tamotsu Fujisawa

  DOI：10.1055/s-1997-6148

  日期：1997.6

  β-Hydroxy ester was formed in high enantiomeric excess by the reaction of ketene silyl acetal with aldehyde in the presence of a chiral Lewis acid prepared from diethylaluminum chloride and chiral diol derived from (+)-camphor.

  在由二乙基氯化铝和从右旋樟脑衍生出的手性二醇制备的手性路易斯酸存在下，烯酮硅乙缩醛与醛反应，生成高对映体过量的β-羟基酯。
• Highly enantioselective synthesis of syn- and anti-propionate aldols without diastereoselection in the chiral oxazaborolidinone-promoted aldol reaction with a silyl ketene acetal derived from ethyl 2-(methylthio)propionate
  作者：Mostofa Abu Hena、Saori Terauchi、Chul-Sa Kim、Michio Horiike、Syun-ichi Kiyooka

  DOI：10.1016/s0957-4166(98)00159-1

  日期：1998.6

  α-methylthio group were obtained in good yields with high enantioselectivities in the chiral oxazaborolidinone-promoted aldol reactions of a novel silyl ketene acetal, derived from ethyl 2-(methylthio)propionate, with aldehydes. Subsequent desulfurization resulted in an effective preparation of essentially enantiopure syn- and anti-propionate aldols which were separable.

  在由2-（甲硫基）丙酸乙基酯衍生的新型甲硅烷基乙烯酮缩醛的手性氧杂硼硼烷酮促进的醛醇缩合反应中，以高收率和高对映选择性获得了包含α-甲硫基的顺式和反式醛醇产物的混合物。醛。随后的脱硫导致有效制备基本上可分离的基本上对映纯的顺式和反丙酸的羟醛。