Synthesis Of Adamantine Tetraone Precursors

Adamantanones are important class of organic intermediates since they can undergo acylation, halogenation, nitration to prepare a number of functional derivatives, such as pharmaceuticals, feedstuffs and new materials. So it is theoretically and applicably important to synthesize the adamantanones.In this article, cyclohexane-1,3-dione was selected as the original substrate to synthesize bicyclo[3.3.1]nonane-2,6,9-trione. The first method afforded bicyclo[3.3.1]nonane-2,6,9-trione in a total yield of43%via Michael addition, intermolecular Aldol condensation and oxidation. The second method gave target product in20%yield via a one-pot process including formation of enamine with morpholine and cyclization with acrylic ethyl ester. The third method also used cyclohexane-1,3-dione and acrylic ethyl ester as start materials and resulted bicyclo[3.3.1]nonane-2,6,9-trione with a high total yield of83%via Michael addition and intermolecular C-acylation. Structures of the compounds were characterized and confirmed by1H-NMR,13C-NMR and IR. The route has not been reported. Furthermore, the third method has outstanding advantadges such as simple operation, easy to workup procedure and high yield. It provides a simple and effective method to form the skeleton construct of bicyclic [3.3.1] nonane. The attempt to prepare adamantine-2,4,6,8-tetraone from bicyclo[3.3.1]nonane-2,6,9-trione was failed.1,5-cyclooctadiene was used to undergo addition with borane and then oxidation to generated1,5-cyclooctanedione, which was formated with ethyl formate to generated2-formyl-1,5-cyclooctanedione. Proline-catalyzed intramoleculare aldol condensation was carried out to afford9-hydroxybicyclo[3.3.1]nonane-2,6-dione. Then, formylation and intramolecular aldol condensation were repeated one more time to give4,8-dihydroxyadamantane-2,6-dione. Finally,2,2,6,6-diethylenedioxyadamantane-4,8-dione, a derivative of adamantine-2,4,6,8-tetraone, was obtained via ketalization and oxidation with a total yield of30.1%. Structures of the compounds were characterized and confirmed by1H-NMR,13C-NMR and IR. The novel compound2,2,6,6-diethylenedioxyadamantane-4,8-dione can be further used to generate multi-substituted adamantane derivatives. This synthetic route is simple and efficient for handling and workup. It is valuable for the construction of other adamantane skeletions.