3-(4-甲基苯基)-3-苯基丙酸甲酯 | 23426-02-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-(4-甲基苯基)-3-苯基丙酸甲酯
• 英文名称: methyl 3-phenyl-3-(p-tolyl)propanoate
• 英文别名: Methyl 3-(4-methylphenyl)-3-phenylpropanoate
• CAS: 23426-02-0
• 化学式: C₁₇H₁₈O₂
• 分子量: 254.329
• InChiKey: YEHCQKPAKRUSSO-UHFFFAOYSA-N

物化性质

• 沸点：
  185-187 °C(Press: 5 Torr)
• 密度：
  1.0786 g/cm3

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 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-(4-甲基苯基)-3-苯基丙酸甲酯 在 aluminum (III) chloride 、 lithium aluminium tetrahydride 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 41.0h， 生成 托普帕敏
  参考文献：
  名称：

  Construction of 3-arylpropylamines using Heck arylations. The total synthesis of cinacalcet hydrochloride, alverine, and tolpropamine

  摘要：

  New synthetic routes toward the commercial drugs cinacalcet hydrochloride, alverine, and tolpropamine were developed using a Heck-Matsuda arylation as the key-step. Several reaction conditions were evaluated for the Heck-Matsuda reaction using allylamine derivatives and arenediazonium salts. For cinacalcet hydrochloride, N-formylamide provided the best result, furnishing the synthetic target in a very high overall yield (75% over five steps). For alverine, the best results were obtained using a double Heck-Matsuda strategy, providing alverine in an excellent overall yield (69%) from N-acetyl diallylamine in three steps. Tolpropamine was synthesized in a 46% yield over five steps using an efficient reductive Heck-Matsuda arylation between p-bromo-methylcinnamate with 3-chloro tolyldiazonium salt, generating the beta,beta-diaryl propionate that was converted to tolpropamine. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.10.014
• 作为产物：
  描述：

  苯甲醛 在 chlorobis(ethylene)rhodium(I) dimer 、 C₄₇H₅₅O₇P 、 sodium hydride 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 mineral oil 为溶剂， 反应 24.33h， 生成 3-(4-甲基苯基)-3-苯基丙酸甲酯
  参考文献：
  名称：

  芳基硼酸到3-芳基丙烯酸酯的Rh催化不对称共轭加成：（R）-Tolterodine的对映选择性合成

  摘要：

  脱氧胆酸衍生的亚萘基亚磷酸酯可将芳基硼酸高度对映体的Rh催化的Rh催化共轭加成到3-芳基丙酸酯中，为合成生物活性化合物提供了有用的手性结构单元。该协议已成功应用于抗毒蕈碱药物（R）-托特罗定的对映选择性合成。

  DOI：

  10.1002/ejoc.201801690

文献信息

• A Conjugate Addition of Arylboronic Acids to<i>α,β</i>-Unsaturated Carbonyl Compounds Catalyzed by 2<i>β</i>-CD-[Rh(OH)(cod)]₂or [RhCl(cod)]₂in a Single Aqueous Medium
  作者：Ryoh Itooka、Yuki Iguchi、Norio Miyaura

  DOI：10.1246/cl.2001.722

  日期：2001.7

  The rhodium-catalyzed conjugate addition of tolylboronic acid to α,β-unsaturated ketones, esters or amides was carried out in water. [RhCl(cod)]2 and 2β-cyclodextrin-[Rh(OH)(cod)]2 complexes were found to catalyze the reaction efficiently in a single aqueous medium.

  在水相中进行了铑催化的甲苯基硼酸与α,β-不饱和酮、酯或酰胺的结合加成反应。研究发现，[RhCl(cod)]2和2β-环糊精-[Rh(OH)(cod)]2复合物能够高效催化该反应，在单一水相介质中进行。
• Rhodium-Catalyzed 1,4-Addition of Arylboronic Acids to α,β-Unsaturated Carbonyl Compounds:  Large Accelerating Effects of Bases and Ligands
  作者：Ryoh Itooka、Yuki Iguchi、Norio Miyaura

  DOI：10.1021/jo0207067

  日期：2003.7.1

  phosphine derivatives. The reaction was further accelerated in the presence of KOH, thus allowing the 1,4-addition even at 0 degrees C. A cationic rhodium(I)-(R)-binap complex, [Rh(R-binap)(nbd)]BF(4), catalyzed the reaction at 25-50 degrees C in the presence of Et(3)N with high enantioselectivities of up to 99% ee for alpha,beta-unsaturated ketones, 92% for aldehydes, 94% for esters, and 92% for amides.

  重新研究了铑（I）催化的芳基硼酸向α，β-不饱和羰基化合物的1,4-加成反应中的配体和碱的影响，以在温和的条件下进行该反应。与相应的铑-acac或-氯配合物及其膦相比，具有1,5-环辛二烯（鳕鱼）和羟基配体如[RhOH（cod）]（2）的铑（I）配合物表现出优异的催化剂活性。衍生品。在KOH的存在下，反应进一步加速，因此甚至在0摄氏度下也可以进行1,4-加成。阳离子铑（I）-（R）-双酚络合物[Rh（R-binap）（nbd）] BF（4）在Et（3）N存在的情况下，在25-50摄氏度的条件下催化反应，对于α，β-不饱和酮，对映选择性高达99％ee，对于醛，对于醛而言，高达92％，对于酯而言，高达94％，酰胺为92％。
• Ligand-Free Nickel-Catalysed 1,4-Addition of Arylboronic Acids to α,β-Unsaturated Carbonyl Compounds
  作者：Wen Chen、Lu Sun、Xi Huang、Jiayi Wang、Yanqing Peng、Gonghua Song

  DOI：10.1002/adsc.201400761

  日期：2015.5.4

  catalytic system has been developed for the 1,4‐addition of arylboronic acids to α,β‐unsaturated carbonyl compounds. With catalyst loadings of 1–2 mol%, a series of 1,4‐adducts from chalcones and cinnamates was obtained in moderate to excellent yields within 5–30 min under a nitrogen atmosphere and microwave irradiation. The 1,4‐addition of arylboronic acids to acrylates is less efficient.

  已开发出一种简单有效的不含配体的镍基催化体系，用于将芳基硼酸1,4-加成到α，β-不饱和羰基化合物上。当催化剂负载量为1-2 mol％时，在氮气氛和微波辐射下5-30分钟内，从查耳酮和肉桂酸盐中获得了一系列1,4-加合物。芳基硼酸与丙烯酸酯的1,4加成效率较低。
• Rh-catalyzed 1,4-addition of triallyl(aryl)silanes to α,β-unsaturated carbonyl compounds
  作者：Toshiyuki Kamei、Mizuho Uryu、Toyoshi Shimada

  DOI：10.1016/j.tetlet.2016.03.002

  日期：2016.4

  4-addition of triallyl(aryl)silane to α,β-unsaturated carbonyl compounds was developed. Triallyl(aryl)silanes were used as air- and moisture-stable silicon nucleophiles. Allylsilanes were converted to silanols in situ and underwent transmetalation. This method can accept a wide range of functionalized triallyl(aryl)silane and α,β-unsaturated carbonyl compounds.

  开发了Rh催化的三烯丙基（芳基）硅烷向α，β-不饱和羰基化合物的1,4-加成反应。三烯丙基（芳基）硅烷被用作对空气和水分稳定的硅亲核试剂。将烯丙基硅烷原位转化为硅烷醇并进行金属转移。该方法可以接受各种官能化的三烯丙基（芳基）硅烷和α，β-不饱和羰基化合物。
• Asymmetric 1,4-Addition of Arylboronic Acids to α,β-Unsaturated Esters Catalyzed by Dicationic Palladium(II)-Chiraphos Complex for Short-Step Synthesis of SmithKline Beecham’s Endothelin Receptor Antagonist
  作者：Norio Miyaura、Takashi Nishikata、Shunsuke Kiyomura、Yasunori Yamamoto

  DOI：10.1055/s-2008-1078259

  日期：——

  An asymmetric 1,4-addition of arylboronic acids to RCH=CHCO2Ar (Ar = Ph or 4-acetylphenyl) was carried out at 50 ˚C in aqueous acetone in the presence of [Pd(chiraphos)(PhCN)2](SbF6)2. The reaction gave optically active β-aryl esters in up to 98% ee. The protocol provided a simple access to an endothelin receptor antagonist reported by SmithKline Beecham.

  在[Pd(chiraphos)(PhCN)2](SbF6)2 的存在下，在 50 ℃ 的丙酮水溶液中进行了芳基硼酸与 RCH=CHCO2Ar （Ar = Ph 或 4-乙酰苯基）的不对称 1,4-加成反应。反应生成了具有光学活性的δ-芳基酯，ee值高达 98%。该方案为 SmithKline Beecham 公司报告的内皮素受体拮抗剂提供了一个简单的途径。