A new development in radical cyclization reaction by using captodative effect by heteroatoms

利用杂原子俘获效应自由基环化反应的新进展

• 批准号: 16550041
• 负责人: KAMIMURA Akio
• 金额: $ 2.3万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16550041/
• 关键词: radical cyclization; exo; endo selectivity; neophyl rearrangement; reaction rate; bezazepines; endo; exo選択性; 立体障害

In this research program, we have found the following things :1)The 7-edno selective radical cyclization, which we have found and utilized for the synthesis of benzazepine derivatives, was governed not by the steric effects but the neophyl rearrangement of 6-exo radical that was initially formed in the cyclization process. Our kinetic study revealed that the rate constant of the neophyl rearrangement was estimated about 100 times smaller than the rate constant of hydrogen abstraction from tributyltin hydride by alkyl radical. This reflects that virtually no rearrangement took place and a mixture of 6-exo and 7-endo adducts was obtained if the concentration of tin hydride was 10^<-1> M level. The syringe-pump technique kept the concentration of tin under 10^<-5> M level which suppressed direct hydrogen abstraction of 6-exo radical and led the neophyl rearrangement proceeded to give 7-endo radical. We have also revealed the rearrangement is irreversible and one way from 6-exo to 7-endo. This may be due to highly stabilization on 7-endo radical as well as kinetic reason in which the radical center of the 7-endo radical is too far to attack the aromatic ring. There should be several effects for stabilization of 7-endo radical, among which the captodative effects is the one. So we concluded that the neophyl rearrangement and captodative effect, both of which were seldom used in organic synthesis, would be a useful controlling factors to develop a new selective synthetic methodologies.2)To develop a new synthetic method to prepare alpha-thio acrylate derivatives, we have examined several reactions that includes the Mannich reaction and the Baylis-Hillman reaction.

在该研究计划中，我们发现了以下内容：1）我们发现并利用了7-EDNO选择性自由基环化，并用于合成苯并氮衍生物，不是由空间效应来控制的，而是由6-EXO激进分析的Neophyl Artrangement控制，在周期化过程中最初形成。我们的动力学研究表明，估计烷基氢化烷基通过烷基自由基氢化氢的氢抽象的速率常数估计估计近100倍。这反映出几乎没有重新排列，如果hydride的浓度为10^<-1> m，则获得了6-EXO和7次加合物的混合物。注射器泵技术将TIN的浓度保持在10^<-5> m的水平下，从而抑制了6-EXO自由基的直接氢气，并导致Neophyl重排以获得7个自由基。我们还揭示了重排是不可逆的，从6-EXO到7-Endo是一种方式。这可能是由于在7-内部自由基和动力学原因上高度稳定，其中7-阶段的自由基中心太远，无法攻击芳族环。稳定7-末日自由基应该有几种效果，其中捕贴效应是一种。因此，我们得出的结论是，在有机合成中很少使用的近苯基重排和捕贴作用将是开发一种新的选择性合成方法的有用控制因素。2）开发一种新的合成方法来制备α-thio thio丙烯酸酯衍生物，我们检查了几个反应，其中包括Mannich-hiris-Hill的反应。