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  • 摘要
  • 摘要
  • 引言
  • 研究方案
  • 结果
  • 讨论
  • 披露声明
  • 致谢
  • 材料
  • 参考文献
  • 转载和许可

摘要

Ionic liquids (ILs) mediate fast, simple and cheap access to 1,6-ketoesters in high diastereoselectivities and good yields. The reaction protocol is robust and the 1,6-ketoesters can be obtained in gram scale after a simple filtration protocol. Moreover, the 1,6-ketoesters are potent gelators in hydrocarbon solvents.

摘要

In organic chemistry ionic liquids (ILs) have emerged as safe and recyclable reaction solvents. In the presence of a base ILs can be deprotonated to form catalytically active N-Heterocyclic Carbenes (NHCs). Here we have used ILs as precatalysts in the addition of α,β-unsaturated aldehydes to chalcones to form 1,6-ketoesters, incorporating an anti-diphenyl moiety in a highly stereoselective fashion. The reaction has a broad substrate scope and several functional groups and heteroaromatics can be integrated into the ketoester backbone in generally good yields with maintained stereoselectivity. The reaction protocol is robust and scalable. The starting materials are inexpensive and the products can be obtained after simple filtration, avoiding solvent-demanding chromatography. Furthermore, the IL can be recycled up to 5 times without any loss of reactivity. Moreover, the 1,6-ketoester end product is a potent gelator in several hydrocarbon based solvents. The method enables rapid access to and evaluation of a new class of low molecular weight gelators (LMWGs) from recyclable and inexpensive starting materials.

引言

figure-introduction-63

（以上）的1,6-酮酯三组分合成:一类新的低分子量胶凝剂。

离子液体（离子液体）具有高稳定性，低挥发性，不可燃性，并因此呈现关注，因为安全的反应介质和理想的溶剂进行回收。1-3二烷基咪唑鎓是一个特定类型的离子液体，在碱的存在下可以去质子化，以使一个N-杂环卡宾（NHC）。4在有机催化的领域中，的NHCs，根据不同的反应路径操作时，已经被广泛的使用在广泛的通用反应。5-11

尽管如此，ILS和CC键formin之间的连接摹NHC催化相对未开发的。尽管如此，从的NHCs离子液体衍生已经报道了催化CC键形成反应，如苯偶姻缩合和施德达反应。12-22。例如，Davis等人已经表明，从N-烷基thiazoliums衍生离子液体作为在预催化剂形成苯甲醛安息香12

最近，Chen和同事扩展使用基于IL咪唑这个概念，1-乙基-3-甲基咪唑鎓乙酸盐（EMIMAc），对5-羟甲基糠醛（HMF）执行安息香缩合以生成5,5' -二（羟甲基）furoin（DHMF）。23由于离子液体可以买到，报价产生NHC的的一种廉价的方式，我们有兴趣在研究什么其他类型的反应，离子液体可以执行。为此，我们发现，二烷基咪唑鎓可有效用作在正规共轭additi预催化剂上的不饱和醛以查耳酮（图1），得到1,6-酮酯。最有效的IL，EMIMAc，促进肉桂醛和查尔之间的高立体选择性反应。发生反应以高偏爱反 -非对映和1,6-酮酯可以分离在产率高达92％。24,25,26

figure-introduction-1177
图1:IL-介导的三组分，立体选择性加成肉桂醛以查耳酮。

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研究方案

甲基-6-氧代-3,4,6- triphenylhexanoate 1.革兰氏规模合成

  1. 干1-乙基-3-甲基咪唑鎓乙酸盐（EMIMAc）在10毫巴，40℃下1小时，在旋转蒸发器的圆底烧瓶中。
  2. 添加2.1克干燥EMIMAc和1.0克1,3-二苯基-2-丙烯-1-酮向100毫升圆底烧瓶配备有磁力搅拌器。
  3. 添加2.019毫升甲醇和2.3克肉桂烧瓶中。
  4. 在室温（22℃）搅拌1分钟溶解在60毫升二氯甲烷的混合物中。
  5. 接着添加0.37 ml的1.8二氮杂二环[5.4.0]十一-7-烯（DBU）到搅拌的混合物（步骤1.4）和帽的圆底烧瓶中。
  6. 搅拌，在500rpm在室温（22℃）的速度一磁力搅拌棒。
  7. 检查用 1 H-NMR。24查找在7.8 ppm的区域中的查耳酮的双键消失反应完成。
  8. 当该反应达到完成除去挥发旋转蒸发器上在10毫巴，20℃下进行15分钟。
  9. 加入50毫升甲醇向残余物通过有磁性搅拌棒搅拌以溶解EMIMAc。
  10. 通过用磁力搅拌棒搅拌下剧烈在750 rpm的速度为30分钟，除去从烧瓶壁上的固体。如果有必要，用刮刀从墙上去除剩余的固体。
  11. 过滤器玻璃料（孔径3）的混合物。
  12. 用另外20ml甲醇洗。如果回收EMIMAc的期望蒸发甲醇滤液。 （步骤2.1）。
  13. 仍然在玻璃料上，轻轻地划分滤饼（从步骤1.11）成较小的块用刮勺和经由粉末漏斗转移到固体预称重的圆底烧瓶中，并在真空下干燥固体。
  14. 称量烧瓶并计算产率。
  15. 由1 H NMR（步骤1.7）分析产物。有报道光谱进行比较。24
EMIMAc的标题"> 2。循环

  1. 在10毫巴减压除去从甲醇混合物（来自步骤1.12）挥发物，在40℃下30分钟。
  2. 通过 1 H NMR和13 C-NMR分析所得的油，以检查EMIMAc存在。24
  3. 使用回收EMIMAc从步骤1.2开始。

3.凝胶

  1. 储备溶液的制备
    1. 加入200毫克甲基-6-氧代-3,4,6- triphenylhexanoate（从步骤1.15的产物）和磁搅拌棒至小瓶的。加入2.0毫升二氯甲烷中，以溶解酮酯。搅拌，直到一切都已经解散。
  2. 凝胶
    1. 加入50毫升庚烷，以500毫升烧杯中。添加1.5 ml的储备溶液的庚烷。搅拌迅速，以确保充分混合，静置而不直至凝胶化发生在环境温度下搅拌。

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结果

如上述例举EMIMAc充当在正规共轭加成α，β不饱和醛与查耳酮一个前段催化剂。其它市售咪唑鎓基的离子液体，例如1-乙基-3-甲基咪唑氯化物（EMIMCl）和1-丁基-3-甲基咪唑氯化物（BMIMCl）也进行了研究，然而，这些反应进行较低的产率，表明乙酸根阴离子可以是为反应性（ 表1，进入1-3）很重要。27,28 *

*阴离子该反应中的作用是在目前还不清楚?...

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讨论

基于由酮酯3的X射线分析和对所提出的Bode和同事30的机械调查确定反 -构型的下述反应路径建议（图5）。白细胞介素脱质子产生NHC种;所述NHC反应与不饱和醛形成布瑞斯罗夫中间体I中布瑞斯罗夫中间和在跨安息香反应的查耳酮反应形成二烯二。中级II经过转乘船过渡态（TS）的氧Cope重排，设置防取向的手性中心III。互变异构之后，酰基氮鎓IV与甲醇反应来交付产品?...

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披露声明

The authors have nothing to disclose.

致谢

We gratefully acknowledge the Swedish Research Council Formas for generous financial support.

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材料

NameCompanyCatalog NumberComments
1-ethyl-3-methyl imidazolium acetateAldrich51053-100G-FProduced by BASF ≥90%, dried on a rotary evaporated before use (10 mBar, 40 °C, 1 hr)
CAS NUMBER: 143314-17-4
1,3-diphenyl-2-propen-1-oneAldrich11970-100G98.0%
CAS NUMBER: 94-41-7
trans-cinnamaldehyde AldrichC80687-25G99%, stored under nitrogen prior to use
CAS NUMBER: 14371-10-9
1,8-Diazobicyclo[5.4.0]undec-7-eneAldrich139009-25G98%
CAS NUMBER: 6674-22-2
MethanolSigma-Aldrich32213N-2.5Lpuriss. P.a., ACS reagent, reag. ISO, reag. Ph. Eur. ≥99.8% (GC)
CAS NUMBER: 67-56-1
DichloromethaneFischer ChemicalD/1852/17XAnalytic reagent grade, stabilized with amylene
CAS NUMBER: 9/2/1975
n-HeptaneFischer ChemicalH/0160/17XAnalytic reagent grade
CAS NUMBER: 142-82-5

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