(3aS,7aS)-1,3-二[(4-溴苯基)甲基]-2-(2E)-2-丁烯-1-基-2-氯八氢-1H-1,3,2-苯并二氮杂硅杂环戊烯 | 1072220-37-1

• 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: (3aS,7aS)-1,3-二[(4-溴苯基)甲基]-2-(2E)-2-丁烯-1-基-2-氯八氢-1H-1,3,2-苯并二氮杂硅杂环戊烯
• 中文别名: （1S，2S）-（+）-[N，N”-双（4-溴苄基）-1,2-环己烷二氨基][（2E）-2-丁烯-1-基]氯硅烷
• 英文名称: (S,S)-trans EZ-CrotylMix
• 英文别名: (3aS,7aS)-1,3-bis(4-bromobenzyl)-2-((E)-but-2-enyl)-2-chloro-octahydro-1H-benzo[d]-[1,3,2]-diazasilole；(S,S)-1,3-Bis(4-bromobenzyl)-2-chlorooctahydro-2-(2E)-crotyl-1H-1,3,2-benzodiazasilole；(3aS,7aS)-1,3-bis[(4-bromophenyl)methyl]-2-[(E)-but-2-enyl]-2-chloro-3a,4,5,6,7,7a-hexahydrobenzo[d][1,3,2]diazasilole
• CAS: 1072220-37-1
• 化学式: C₂₄H₂₉Br₂ClN₂Si
• 分子量: 568.854
• InChiKey: ZRWSDIWSVXXBNG-KOAGWOQNSA-N

物化性质

• 熔点：
  92-96°C
• 比旋光度：
  +52.9° (c 1.3, CH2Cl2)

计算性质

• 辛醇/水分配系数(LogP)：
  7.59
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,4-bis(benzyloxy)-6-chloro-5-phenylpyridine-3-carbaldehyde 、 (3aS,7aS)-1,3-二[(4-溴苯基)甲基]-2-(2E)-2-丁烯-1-基-2-氯八氢-1H-1,3,2-苯并二氮杂硅杂环戊烯 在 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 48.0h， 以80%的产率得到(1R,2R)-1-(2,4-bis(benzyloxy)-6-chloro-5-phenylpyridin-3-yl)-2-methylbut-3-en-1-ol
  参考文献：
  名称：

  Formal synthesis of TMC-69-6H via a one-pot enantioselective domino proline-mediated aldol/olefin homologation procedure

  摘要：

  Enantioselective synthesis of TMC-69-6H was accomplished from readily accessible pyridone derivative via a domino proline-mediated aldol reaction/olefin homologation, followed by tandem ring-closing and cross metathesis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.11.025
• 作为产物：
  描述：

  对溴苯甲醛 在 sodium tetrahydroborate 、 甲烷磺酸 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 25.0h， 生成 (3aS,7aS)-1,3-二[(4-溴苯基)甲基]-2-(2E)-2-丁烯-1-基-2-氯八氢-1H-1,3,2-苯并二氮杂硅杂环戊烯
  参考文献：
  名称：

  Formal synthesis of TMC-69-6H via a one-pot enantioselective domino proline-mediated aldol/olefin homologation procedure

  摘要：

  Enantioselective synthesis of TMC-69-6H was accomplished from readily accessible pyridone derivative via a domino proline-mediated aldol reaction/olefin homologation, followed by tandem ring-closing and cross metathesis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.11.025

文献信息

• A Highly Stereoselective, Efficient, and Scalable Synthesis of the C(1)–C(9) Fragment of the Epothilones
  作者：Corinne N. Foley、James L. Leighton

  DOI：10.1021/acs.orglett.5b03034

  日期：2015.12.4

  second-generation synthesis of the C(1)–C(9) fragment of the epothilones is reported. The key tandem intramolecular silylformylation/crotylsilylation/“aprotic” Tamao oxidation sequence has been redeveloped as a stepwise intermolecular variant, allowing excellent levels of diastereoselectivity in the crotylation step and proceeds in 50% overall yield on gram scale. An improved synthesis of the homopropargyl

  报道了埃博霉素的C（1）–C（9）片段的第二代合成。关键的串联分子内甲硅烷基甲酰化/巴豆基甲硅烷基化/“非质子” Tamoo氧化顺序已被重新开发为逐步的分子间变体，从而在巴甲酰化步骤中具有极佳的非对映选择性，并以克级计获得了50％的总收率。还描述了高炔丙醇起始原料的改进的合成，其从廉价的起始原料开始以四个步骤进行，并且ee＞ 99％，并且适合于多克规模。
• Enantioselective Allylation of (2<i>E</i>,4<i>E</i>)-2,4-Dimethylhexadienal: Synthesis of (5<i>R</i>,6<i>S</i>)-(+)-Pteroenone
  作者：Petr Koukal、Martin Kotora

  DOI：10.1002/chem.201500050

  日期：2015.5.11

  induction, and catalyst load in comparison to other procedures. The developed methodology was applied in the enantioselective synthesis of (5R,6S)‐(+)‐pteroenone, a defensive metabolite (ichthyodeterrent) of the Antarctic pteropod Clione antarctica.

  烯丙基化，反式-和顺式-（2 crotylation ë，4 ê）-2,4- dimethylhexadienal，代表性α，β，γ，δ不饱和醛，在不同的催化和化学计量的条件下进行。与其他方法相比，有机催化剂TRIP-PA和N，N'-二氧化物催化的反应在收率，不对称诱导和催化剂负载方面提供了最佳结果。所开发的方法应用于（5 R，6 S）-（+）-戊烯酮的对映选择性合成，这是一种南极翼足​​类Clione南极的防御性代谢产物（鱼类去甲脂）。
• Total Synthesis of Amphidinolide X and Its 12<i>Z</i>-Isomer by Formation of the C12-C13 Trisubstituted Double Bond via Ring-Closing Metathesis
  作者：Wei-Min Dai、Jinlong Wu、Yile Chen、Jian Jin、Jianshu Lou、Qiaojun He

  DOI：10.1055/s-2008-1077885

  日期：——

  Amphidinolide X, a 16-membered cytotoxic macro­diolide, and its 12Z-isomer have been synthesized via ring-closing metathesis (RCM) for assembling the C12-C13 trisubstituted double bond. A 29:71 E/Z mixture was obtained from the seco substrate appended with a bulky C8-ODPS group in 50-65% combined yields by using 20 mol% of the second-generation Grubbs initiator and the corresponding indenylidene ruthenium complex. Amphidinolide X and 12Z-isomer exhibit similar cytotoxicity (IC50: 7.6-13.9 µg/mL) against A549, KB, and HL60 cell lines.

  一种 16 元细胞毒性大环内酯 Amphidinolide X 及其 12Z 异构体是通过环闭合偏析 (RCM) 合成的，以组装 C12-C13 三取代双键。通过使用 20 摩尔百分率的第二代格拉布斯引发剂和相应的亚茚基钌络合物，从附加了一个笨重的 C8-ODPS 基团的仲底物中获得了 29:71 的 E/Z 混合物，总产率为 50-65%。蚜虫内酯 X 和 12Z 异构体对 A549、KB 和 HL60 细胞株具有相似的细胞毒性（IC50：7.6-13.9 µg/mL）。
• Beyond the Roche Ester: A New Approach to Polypropionate Stereotriad Synthesis
  作者：Corinne N. Foley、James L. Leighton

  DOI：10.1021/ol500051e

  日期：2014.2.21

  An efficient, step-economical, and scalable approach to the synthesis of polypropionate stereotriads has been developed. Either 2-butyne or propyne is subjected to rhodium-catalyzed silylformylation and in situ crotylation of the resulting aldehydes. Tamao oxidation under either “standard” conditions or “aprotic” conditions then delivers the completed stereotriads in a three-step, two-pot sequence

  已开发出一种高效、经济且可扩展的方法来合成聚丙酸酯立体三联体。2-丁炔或丙炔经过铑催化的甲硅烷基甲酰化和所得醛的原位巴豆化。Tamao 在“标准”条件或“非质子”条件下氧化，然后以三步两锅的顺序提供完整的立体三联体。与经典的罗氏酯方法相比，α-立体中心是“免费”获得的。
• Direct and highly regioselective and enantioselective allylation of β-diketones
  作者：Wesley A. Chalifoux、Samuel K. Reznik、James L. Leighton

  DOI：10.1038/nature11189

  日期：2012.7

  A simple, regioselective and enantioselective method for allylating β-diketones has been developed, significantly expanding the pool of easily accessible enantiomerically enriched and functionally complex tertiary carbinols. The enantioselective allylation of ketones represents a problem of fundamental importance in asymmetric reaction design, especially given that only a very small number of methods can generate tertiary carbinols. In this manuscript, the authors describe a simple, regioselective and enantioselective method for allylating β-diketones. This reaction significantly expands the pool of enantiomerically enriched and functionally complex tertiary carbinols that can be easily accessed and also overturns more than a century of received wisdom regarding the reactivity of β-diketones. The enantioselective allylation of ketones is a problem of fundamental importance in asymmetric reaction design, especially given that only a very small number of methods can generate tertiary carbinols. Despite the vast amount of attention that synthetic chemists have given to this problem1,2,3,4,5,6,7,8, success has generally been limited to just a few simple ketone types. A method for the selective allylation of functionally complex ketones would greatly increase the utility of ketone allylation methods in the chemical synthesis of important targets. Here we describe the operationally simple, direct, regioselective and enantioselective allylation of β-diketones. The strong tendency of β-diketones to act as nucleophilic species was overcome by using their enol form to provide the necessary Brønsted-acid activation. This reaction significantly expands the pool of enantiomerically enriched and functionally complex tertiary carbinols that may be easily accessed. It also overturns more than a century of received wisdom regarding the reactivity of β-diketones.

  一种简单的、区域选择性和对映选择性的烯丙基化β-二酮方法已被开发出来，显着扩大了易于获得的对映体丰富且功能复杂的叔醇的库。酮的对映选择性烯丙基化是不对称反应设计中的一个非常重要的问题，特别是考虑到只有极少数的方法可以生成叔醇。在这篇手稿中，作者描述了一种简单的区域选择性和对映选择性烯丙基化 β-二酮的方法。该反应显着扩大了对映异构体丰富且功能复杂的叔醇库，这些叔醇可以很容易地获得，并且还颠覆了一个多世纪以来关于β-二酮反应性的公认观点。酮的对映选择性烯丙基化是不对称反应设计中一个非常重要的问题，特别是考虑到只有极少数的方法可以生成叔醇。尽管合成化学家对这个问题给予了大量的关注1,2,3,4,5,6,7,8，但成功通常仅限于几种简单的酮类型。功能复杂酮的选择性烯丙基化方法将大大增加酮烯丙基化方法在重要靶标化学合成中的效用。在这里，我们描述了操作简单、直接、区域选择性和对映选择性的β-二酮烯丙基化。通过使用烯醇形式提供必要的布朗斯台德酸活化，克服了β-二酮作为亲核物质的强烈倾向。该反应显着扩大了对映体富集且功能复杂的叔醇库，并且可以很容易地获得。它还颠覆了一个多世纪以来关于β-二酮反应性的公认观点。