Studies of Stereoceiective Preparation of 7-Membered Heterocycles Utilyzing Intramolecular

分子内立体定向制备七元杂环的研究

基本信息

批准号：
09650940
负责人：
NOGUCHI Michihiko
金额：
$ 2.18万
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：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09650940/
关键词：
azepine-ring formation intramolecular type III ene reaction carbonyl ene reaction imine ene reaction olefin ene reaction 1,6-hydrogen shift conjugated azomethine ylide 1,7-electrocyclization アゼピン環形成反応

项目摘要

The thermal reaction of the α,β-unsaturated aldehydes bearing an (alk-2-enyl) amino moiety at the β-position gave the azepine derivatives in good to excellent yields. When these groups were a part of heterocycles, the azepine derivatives fused by the heterocyclic systems were formed. The imines of the aldehydes also afforded the azepine derivatives. The vinyl substrates, obtained by the condensation reaction of the aldehydes with activated methylene compounds, gave the azepine derivatives and/or hetero Diels-Alder adducts depending on the kind of the substituents both on the vinyl and alkenyl parts. The similar reactions of β-(alk-2-enyl) aminoacroleins gave the simple azepine derivatives. The reactivity for the azepine-ring formation of the acroleins depended on the substituent (R) on the α-position; the acrolein bearing methoxycarbonyl group at the α-position is still obscure, we suggest that the steric bulkyness of the α-substituents should affect on the cyclization step.These azepine-ring formation could be regarded as the intramolecular carbonyl, imine, and olefin ene reactions classified as a Type III ene reaction. Therein, the reactions proceeded in a highly stereoselective manner; when the substrates having alkenylamino moieties with the E-configuration were allowed to react, the azepine derivatives with the 4,5-cis configuration were obtained. The PM3 molecular orbital calculations of the model reactions suggest that the azepine-ring formation is constituted of two consecutive orbital-allowed reactions; 1,6-shift of the allylic hydrogen of the alkenylamino moiety to the carbonyl oxygen (or immune nitrogen) leading to conjugated azomethine ylides and 1,7-electrocyclization of the azomethine ylides.In order to obtain further informations on the reaction mechanism, both imine and carbonyl ene reactions using the aldehydes bearing a chiral center at the alkenylamino moiety have performed a self-immolating chirality transfer to the azepine ring.

在 β 位带有（烷-2-烯基）氨基部分的 α,β-不饱和醛的热反应以良好至优异的产率产生氮杂卓衍生物。当这些基团是杂环的一部分时，氮杂卓衍生物稠合。醛的亚胺也形成了氮杂环庚烷衍生物，通过醛与活化的亚甲基的缩合反应获得。化合物，根据乙烯基和烯基部分上的取代基的类型，得到氮杂环庚烷衍生物和/或杂狄尔斯-阿尔德加合物。β-(烷基-2-烯基)氨基丙烯醛的类似反应得到简单的氮杂环庚烷衍生物。丙烯醛的吖庚因环的形成依赖于α位上带有甲氧基羰基的丙烯醛的取代基(R)； α-位仍然不清楚，我们认为α-取代基的空间体积应该影响环化步骤。这些氮杂环的形成可以被视为分子内羰基、亚胺和烯烃反应，被归类为III型烯其中，当使具有E-构型的烯基氨基部分的底物反应时，反应以高度立体选择性的方式进行；模型反应的 PM3 分子轨道计算表明，氮杂环的形成是由两个连续的轨道允许反应组成；从烯基氨基获得的烯丙基氢的 1,6-位移。部分与羰基氧（或免疫氮）连接，导致共轭偶氮甲碱叶立德和偶氮甲碱叶立德的1,7-电环化。为了进一步获得关于反应机理的信息，使用在烯基氨基部分带有手性中心的醛的亚胺和羰基反应都进行了自毁手性转移到氮杂环。