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。烯酮与乙醛在同一分子中与SmI_2发生反应，根据反应条件的不同，可顺利生成环化的双环酮。在室温或更低温度下，THF中不使用添加剂（即SmI_2）时，产物中羟基与接点取代基呈顺式关系。而当甲醇作为质子源存在时，羟基与结合部取代基相互发生反式关系。这些立体化学是通过测量NOEs，在基本条件下进行平衡实验，在某些情况下通过x射线晶体学分析建立的。6元环和7元环的环化在6元三角或7元三角环化模式下顺利进行。然而，由于Baldwin规则的关系，5元环很难实现。我们已经证明了这种合成方法可以得到良好到中等产量的苯二酮、过氢萘烯酮和过氢唑烯酮。该方法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.