Synthetic Studies ofcis-3a-Aryloctahydroindole Derivatives by Copper-Catalyzed Cyclization ofN-Allyltrichloroacetamides: Facile Construction of Benzylic Quaternary Carbons by Carbon−Carbon Bond-Forming Reactions

Cyclization of N -(2-aryl-2-cyclohexen-1-yl)trichloroacetamides by a copper catalyst was investigated. It is crucially important for successful cyclization under mild conditions that alkoxycarbonyl groups are introduced to the nitrogen atom of the N -allyltrichloroacetamides as well as that CuCl(bipyridine) is used as the catalyst. Three compounds, N -(2-phenyl-2-cyclohexen-1-yl)-, N -[2-(3,4-dimethoxyphenyl)-2-cyclohexen-1-yl]-, and N -[2-(3,4-methylenedioxyphenyl)-2-cyclohexen-1-yl]trichloroacetamides, where the Cbz or MeO 2 C− group was attached to the nitrogen atom, were instantly converted to the corresponding trichlorinated cis -3a-aryloctahydroindol-2-ones in high yields at room temperature. The reactions offer a facile access to alkaloid skeletons such as mesembrines and crinines; as the simplest examples, total synthesis of (±)-mesembrane and (±)-crinane was accomplished. The effect of alkoxycarbonyl substituents in the amide group was compared with that of the methyl substituent. N -Methyl- N -(2-phenyl-2-cyclohexen-1-yl)trichloroacetamide quickly reacted in the presence of CuCl(bipyridine) catalyst; however, the products were a mixture of complicated materials including a small amount of the desired lactam. The role of the alkoxycarbonyl group was discussed in terms of rate of rotation of the N−C bond in the N -allyltrichloroacetamides; variable-temperature NMR studies and X-ray structure determination of related compounds were carried out as supporting evidence.