Development of General Synthetic Method for Bicyclic Compounds by Reductive Cyclization Reactions Using SmI_2

本工作旨在建立用SMI_2还原环化反应合成双环化合物的一般概念。根据所用条件的不同，烯酮与同一分子中的醛与SMI_2顺利地反应生成环状双环酮。当不使用添加剂时，即四氢呋喃中的SMI_2在RT或更低温度下，产物中的羟基与连接取代基之间存在顺式关系。而以甲醇为质子源时，羟基和连接取代基之间存在反式关系。这些立体化学是通过测量NOE，在基本条件下进行平衡实验，在某些情况下通过X射线结晶学分析来建立的。环化成6元环和7元环在6-Endo-Trig或7-Endo-Trig环化模式下顺利进行。然而，5元环很难实现，可能是由于鲍德温规则。我们已经证明了该合成方法以良好到中等的产率合成了氢化吲哚酮、全氢萘二酮和全氢天青酮。这种方法还可以应用于其他类型的双环化合物，这是本实验室未来的计划。

This work aims at establishing a general concept of synthesizing bicyclic compounds by the reductive cyclization reaction using SmI_2. The reaction of an enone with an aldehyde in the same molecule with SmI_2 smoothly occurred to produce cyclized bicyclic ketols depending on the conditions used. When no additive was used, namely SmI_2 in THF at rt or lower temperature, products have cis relationship between a hydroxyl group and a juncture substituent. While in the presence of methanol as a proton source, a hydroxyl group and a juncture substituent have trans relationship each other. These stereochemistries were established by measuring the NOEs, performing the equilibrium experiments under basic conditions, and in some cases by X-ray crystallographic analysis. The cyclization into 6- and 7-membered rings smoothly worked in the 6-Endo-Trig or 7-Endo-Trig mode of cyclization. However, 5-membered rings were difficult to realize presumably due to the Baldwin rule. We have demonstrated the synthetic method into hydrindanones, perhydronaphtahlenones, and perhydroazulenones in good to moderate yields. This method can be applied to another type of bicyclic compounds, which is the future program in this laboratory.