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

在本研究中，我们发现了以下几点：1）在苯并氮杂卓衍生物的合成中，发现并利用的7-外氧自由基选择性环化反应，不是由空间位阻效应控制的，而是由环化反应中最初形成的6-外氧自由基的新叶重排控制的。我们的动力学研究表明，neophyl重排的速率常数估计约100倍，小于由烷基自由基的三丁基氢化锡的氢提取速率常数。这反映出，如果氢化锡的浓度为10 μ M水平，则实际上没有发生重排，并且获得6-外加合物和7-内加合物的混合物<-1>。双泵技术使锡的浓度保持在10 μ M以下<-5>，从而抑制了6-外位自由基的直接夺氢，并使新叶素重排继续生成7-内位自由基。我们还发现重排是不可逆的，从6-exo到7-endo是单向的。这可能是由于7-内自由基的高度稳定性以及7-内自由基的自由基中心太远而不能攻击芳环的动力学原因。7-内自由基的稳定作用应该是多种效应共同作用的结果，其中捕获效应是其中之一。因此，我们认为，在有机合成中很少使用的新酚重排和捕获效应，将是一个有用的控制因素，以开发新的选择性合成方法。2）为了开发一种新的合成方法，我们研究了几种反应，包括Mannich反应和Baylis-Hillman反应，以制备α-硫代丙烯酸酯衍生物。

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.