MODEL STUDIES TOWARD THE SYNTHESIS OF THE LYCOPODIUM ALKALOID, PHLEGMARINE

Model studies were carried out toward the preparation of Lycopodium alkaloids, i.e. the phlegmarines, which contain a trans-decahydroquinoline ring system, The target decahydroquinoline derivative 6 was synthesized stereoselectively in eight steps. The keto aldehyde 10, prepared in three steps from 4-methoxypyridine, was subjected to an acid-catalyzed Robinson annulation reaction to give bicyclic enone 11, Copper-mediated 1,4-addition of [(dimethylphenylsilyl)methyl]magnesium chloride and in situ trapping with N-(5-chloro-2-pyridyl)triflimide provided vinyl triflate 12. Conversion to olefin 16 and subsequent hydrolysis gave amine 20, Stereoselective hydrogenation of 20 over palladium on carbon yielded the trans-decahydroquinoline 6 and its cis isomer 21 in a ratio of 89:11, Arguments involving A((1,3)) strain are given to explain the observed stereoselectivity.