(R)-methyl 2,3-dihydrobenzo[b][1,4]dioxine-2-carboxylate | 650597-67-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (R)-methyl 2,3-dihydrobenzo[b][1,4]dioxine-2-carboxylate
• 英文别名: (R)-(+)-methyl 1,4-benzodioxan-2-carboxylate；(R)-methyl 1,4-benzodioxane-2-carboxylate；methyl (R)-1,4-benzodioxane-2-carboxylate；(R)-methyl 1,4-benzodioxan-2-carboxylate；methyl (3R)-2,3-dihydro-1,4-benzodioxine-3-carboxylate
• CAS: 650597-67-4
• 化学式: C₁₀H₁₀O₄
• 分子量: 194.187
• InChiKey: SNLAAGHHNZECPE-SECBINFHSA-N

物化性质

• 沸点：
  271.0±39.0 °C(Predicted)
• 密度：
  1.245±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-methyl 2,3-dihydrobenzo[b][1,4]dioxine-2-carboxylate 在 二异丁基氢化铝 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以95%的产率得到(S)-2-羟甲基-1,4-苯并二恶烷
  参考文献：
  名称：

  通过Rh催化的不对称氢化反应对映选择手性2-取代的2,3-二氢苯并[1,4]二恶烷衍生物

  摘要：

  成功开发了Rh催化的各种苯并[ b ] [1,4]二恶英衍生物的不对称加氢反应，以使用ZhaoPhos和具有高取代度的ZhaoPhos配体的N-甲基化来制备手性2取代的2,3-二氢苯并[1,4]二恶烷衍生物。收率和出色的对映选择性（高达99％的收率，> 99％的对映体过量（ee），周转数（TON）= 24000）。此外，这种不对称氢化方法作为高达10000吨的关键步骤，已成功地用于开发高效的合成路线，以构建一些重要的生物活性分子，例如MKC-242，WB4101，BSF-190555和（R）-恶唑烷·HCl。

  DOI：

  10.1021/acs.orglett.8b01469
• 作为产物：
  描述：

  1,4-苯并二烷-2-羧酸 在 sodium hydroxide 、 (+)-Dehydroabietylamine ethanoate 、 硫酸 、 原甲酸三甲酯 作用下， 以 甲醇 为溶剂， 反应 12.5h， 生成 (R)-methyl 2,3-dihydrobenzo[b][1,4]dioxine-2-carboxylate
  参考文献：
  名称：

  A short entry to enantiopure 2-substituted 1,4-benzodioxanes by efficient resolution methods

  摘要：

  (R)-1,4-Benzodioxane-2-carboxilic acid (R)-1 was obtained by resolution of the racemic acid 1 with stoichiometric or nonstoichiometric (+)-dehydroabietylamine (+)-2 in high chemical yield and enantiomeric excess. (S)-1 was isolated from the mother liquors of the crystallisation of (R)-1-(+)-2 and its enantiomeric excess maximised by recrystallisation procedures involving a precipitation under kinetic control or, alternatively, by conversion into the methyl ester followed by a single crystallisation. The different mechanisms of the two S enrichments is well explained by the binary phase diagrams of the acid and of the ester, which show that the former is a racemic compound, whereas the latter a conglomerate. The DSC analyses were extended to 2-hydroxymethyl- and 2-mesyloxymethyl-1,4-benzodioxane, establishing that the alcohol forms a racemic compound, while its mesyl ester a conglomerate. On the basis of these results, different resolution strategies can be designed to obtain useful homochiral 2-substituted 1,4-benzodioxanes coupling the resolution of I via diastereomeric salt formation with the enantiomeric enrichments by recrystallisations, preferably of its conglomerate forming derivatives. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2003.09.012

文献信息

• A versatile catalyst system for enantioselective synthesis of 2-substituted 1,4-benzodioxanes
  作者：Eugene Chong、Bo Qu、Yongda Zhang、Zachary P. Cannone、Joyce C. Leung、Sergei Tcyrulnikov、Khoa D. Nguyen、Nizar Haddad、Soumik Biswas、Xiaowen Hou、Katarzyna Kaczanowska、Michał Chwalba、Andrzej Tracz、Stefan Czarnocki、Jinhua J. Song、Marisa C. Kozlowski、Chris H. Senanayake

  DOI：10.1039/c8sc05612a

  日期：——

  We report the synthesis of enantiomerically enriched 1,4-benzodioxanes containing alkyl, aryl, heteroaryl, and/or carbonyl substituents at the 2-position. The starting 1,4-benzodioxines were readily synthesized via ring closing metathesis using an efficient nitro-Grela catalyst at ppm levels. Excellent enantioselectivities of up to 99:1 er were obtained by using the versatile catalyst system [Ir(c

  我们报道了2位含有烷基、芳基、杂芳基和/或羰基取代基的对映体富集的1,4-苯并二恶烷的合成。使用有效的硝基-Grela 催化剂，通过闭环复分解很容易合成起始 1,4-苯并二恶英，浓度为 ppm 水平。通过在 2-取代 1,4-苯并二恶英的不对称氢化中使用多功能催化剂体系 [Ir(cod)Cl] 2 /BIDIME-二聚体，获得了高达 99:1 er 的优异对映选择性。此外，DFT 计算表明该过程的选择性是由质子化步骤控制的；基底上的配位基团可能会改变与催化剂的相互作用，从而导致面选择性的变化。
• Chemoenzymatic synthesis of piperoxan, prosympal, dibozane, and doxazosin
  作者：Abdul Rouf、Pankaj Gupta、Mushtaq A. Aga、Brijesh Kumar、Asha Chaubey、Rajinder Parshad、Subhash C. Taneja

  DOI：10.1016/j.tetasy.2012.10.018

  日期：2012.12

  The synthesis of both enantiomers of 1,4-benzodioxan-2-carboxylic acid 1, a key synthetic intermediate for the therapeutic agents piperoxan, prosympal, dibozane, and doxazosin was achieved with good yields and high enantioselectivities via the Arthrobacter sp. lipase catalyzed kinetic resolution of ester (+/-)-17a. The influence of the co-solvents and the immobilization of the lipase upon kinetic resolution demonstrated that immobilized whole cells, in the presence of n-butanol as a co-solvent, resulted in the optimal resolution of the substrate (ee similar to 99%, E = 535) at 258 mmol (50 g/L) substrate concentration. (C) 2012 Elsevier Ltd. All rights reserved.
• From 2-Aminomethyl-1,4-benzodioxane Enantiomers to Unichiral 2-Cyano- and 2-Carbonyl-Substituted Benzodioxanes via Dichloroamine
  作者：Cristiano Bolchi、Ermanno Valoti、Valentina Straniero、Paola Ruggeri、Marco Pallavicini

  DOI：10.1021/jo500964y

  日期：2014.7.18

  2-Substituted 1,4-benzodioxanes, such as 2-cyano-, 2-methoxycarbonyl-, 2-aminocarbonyl-, and 2-formyl-1,4-benzodioxane, are key synthons that for the most part are never described as enantiomers or are inadequately characterized for enantiomeric purity. They were prepared by quantitative N,N-dichlorination of (R)- and (S)-2-aminomethyl-1,4-benzodioxane and successive functional group conversions in high yields without any racemization of the stereogenic benzodioxane C(2).
• A short entry to enantiopure 2-substituted 1,4-benzodioxanes by efficient resolution methods
  作者：Cristiano Bolchi、Laura Fumagalli、Barbara Moroni、Marco Pallavicini、Ermanno Valoti

  DOI：10.1016/j.tetasy.2003.09.012

  日期：2003.11

  (R)-1,4-Benzodioxane-2-carboxilic acid (R)-1 was obtained by resolution of the racemic acid 1 with stoichiometric or nonstoichiometric (+)-dehydroabietylamine (+)-2 in high chemical yield and enantiomeric excess. (S)-1 was isolated from the mother liquors of the crystallisation of (R)-1-(+)-2 and its enantiomeric excess maximised by recrystallisation procedures involving a precipitation under kinetic control or, alternatively, by conversion into the methyl ester followed by a single crystallisation. The different mechanisms of the two S enrichments is well explained by the binary phase diagrams of the acid and of the ester, which show that the former is a racemic compound, whereas the latter a conglomerate. The DSC analyses were extended to 2-hydroxymethyl- and 2-mesyloxymethyl-1,4-benzodioxane, establishing that the alcohol forms a racemic compound, while its mesyl ester a conglomerate. On the basis of these results, different resolution strategies can be designed to obtain useful homochiral 2-substituted 1,4-benzodioxanes coupling the resolution of I via diastereomeric salt formation with the enantiomeric enrichments by recrystallisations, preferably of its conglomerate forming derivatives. (C) 2003 Elsevier Ltd. All rights reserved.
• Enantioselective Access to Chiral 2-Substituted 2,3-Dihydrobenzo[1,4]dioxane Derivatives through Rh-Catalyzed Asymmetric Hydrogenation
  作者：Xuguang Yin、Yi Huang、Ziyi Chen、Yang Hu、Lin Tao、Qingyang Zhao、Xiu-Qin Dong、Xumu Zhang

  DOI：10.1021/acs.orglett.8b01469

  日期：2018.7.20

  Rh-catalyzed asymmetric hydrogenation of various benzo[b][1,4]dioxine derivatives was successfully developed to prepare chiral 2-substituted 2,3-dihydrobenzo[1,4]dioxane derivatives using ZhaoPhos and N-methylation of ZhaoPhos ligands with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess (ee), turnover number (TON) = 24 000). Moreover, this asymmetric hydrogenation

  成功开发了Rh催化的各种苯并[ b ] [1,4]二恶英衍生物的不对称加氢反应，以使用ZhaoPhos和具有高取代度的ZhaoPhos配体的N-甲基化来制备手性2取代的2,3-二氢苯并[1,4]二恶烷衍生物。收率和出色的对映选择性（高达99％的收率，> 99％的对映体过量（ee），周转数（TON）= 24000）。此外，这种不对称氢化方法作为高达10000吨的关键步骤，已成功地用于开发高效的合成路线，以构建一些重要的生物活性分子，例如MKC-242，WB4101，BSF-190555和（R）-恶唑烷·HCl。