Synthesis of Pharmacologically Active Natural Products using Radical Translocation/cyclization Reactions

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The scope and limitations of tributyltin hydride (Bu_3SnH)-mediated radical translocation/cyclization reactions and an application to the synthesis of pharmacologically active natural products have been investigated. The results obtained were as follows :(1) Bu_3SnH-mediated radical translocation/cyclization reactions of methyl 1-(o-iodobenzoyl)-2-[4-(trimethylsilyl) but-3-ynyl]-piperi-dine-2-carboxylate and 1-(o-iodobenzoyl)-2-methyl-2-[4-(trimethyl-silyl)but-3-ynyl] piperidine-2-carboxylate proceeded in a regio-selective 6-exo-dig manner to give 9-azabicyclo [3.3.1] nonanes in high yield as a 1 : 1 diastereomeric mixture in both cases. 1-(o-Iodobenzoyl)-2-[4-(trimethylsilyl) but-3-ynyl] piperidine also afforded the 9-azabicyclo [3.3.1] nonane (65%), along with the hexahydropyrido [2, 1-a] isoindolone derivative (23%). Conversion of the 9-azabicyclo [3.3.1] nonane to (±)-euphococcinine was also examined.(2) The reaction of 1-(o-iodobenzoyl)-4-[3-(trimethylsilyl) prop-2-ynyl] piperidine afforded the isomeric 2-azabicyclo [3.2.1] octanes in 34 and 51% yield, along with a trace amount of the reduction product. On the other hand 1-(o-iodobenzoyl)-4-[4-(trimethyl-silyl) but-3-ynyl] piperidine proceeded more slowly to give the 2-azabicyclo [3.3.1] nonane (morphan) in 20% yield as a diastereomeric mixture. In the latter case the reduction product was obtained as a major product in 75% yield.(3) Both 1-[3-(trimethylsilyl) prop-2-ynyl]-and 1-[4-(trimethyl-silyl) but-3-ynyl]-2-(o-iodobenzoyl)-1, 2, 3, 4-tetrahydroiso-quinolines, upon treatment with Bu_3SnH, underwent smoothly either a 5-exo-dig or 6-exo-dig cyclization to give the isomeric 6, 7, 8, 9-tetrahydro-5H-benzocyclohepten-5, 8-imines (95%) and 5, 6, 7, 8, 9, 10-hexahydrobenzocycloocten-5, 9-imines (65%), respectively.