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

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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.