• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Chemistry: A European journal >Asymmetric Sulfonium Ylide Mediated Cyclopropanation: Stereocontrolled Synthesis of (+)-LY354740
【24h】

Asymmetric Sulfonium Ylide Mediated Cyclopropanation: Stereocontrolled Synthesis of (+)-LY354740

机译：不对称叶立德S介导的环丙烷化：（+）-LY354740的立体控制合成

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The reaction of ester-stabilized sulfonium ylides with cyclopente-none to give (+)-5 ((1S,5R,6S)-ethyl 2-oxobicyclo[3.1.0]hexane-6-carboxylate),an important precursor to the pharmacologically important compound (+)-LY354740,has been studied using chiral sulfides operating in both catalytic (sulfide,Cu(acac)_2,ethyl diazoace-tate,60 deg C) and stoichiometric modes (sulfonium salt,base,room temperature).It was found that the reaction conditions employed had a major influence over both diastereo- and enantio-selectivity.Under catalytic conditions,good enantioselectivity with low dia-stereoselectivity was observed,but under stoichiometric conditions low enantioselectivity with high diastereo-selectivity was observed.When the stoichiometric reactions were conducted at high dilution,diastereoselectivity was reduced.This indicated that base-mediated betaine equilibration was occurring (which is slow relative to ring closure at high dilution).Based on this model,conditions for achieving high enantioselectivity were established as follows: use of a preformed ylide,absence of base,hindered ester (to reduce ylide-mediated betaine equilibration),and low concentration.Under these conditions high enantioselectivity (95% ee) was achieved,albeit with low diastereocontrol.Our model for selectivity has been applied to other sulfonium ylide mediated Cyclopropanation reactions and successfully accounts for the diastereoselectivity observed in all such reported reactions to date.
机译：酯稳定的鎓烷基化物与环戊烯酮不发生反应，可生成（+）-5（（1S，5R，6S）-乙基2-氧代双环[3.1.0]己烷-6-羧酸盐），这是药理学上重要的前体使用手性硫化物研究了重要的化合物（+）-LY354740，该手性硫化物在催化（硫化物，Cu（acac）_2，重氮酸乙酯，60℃）和化学计量模式（s盐，碱，室温）下运行。已发现所采用的反应条件对非对映选择性和对映选择性均具有重大影响。在催化条件下，观察到良好的对映选择性，低对映选择性，但在化学计量条件下，对映选择性低，对映选择性高。在高稀释度下进行化学计量反应，降低了非对映选择性。这表明发生了碱介导的甜菜碱平衡（相对于高稀释度下的闭环反应缓慢）。建立对映体选择性如下：使用预先形成的叶立德，不存在碱，受阻的酯（以减少叶立德介导的甜菜碱平衡）和低浓度。在这些条件下，尽管非对映异构控制很低，但仍实现了高对映体选择性（95％ee）。我们的选择性模型已应用于其他由叶立德介导的环丙烷化反应，并成功地解释了迄今为止在所有此类报道的反应中观察到的非对映选择性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号