Cobalt-mediated [2+2+2] cycloaddition of alkynes to the enamine double bond: A formal total synthesis of γ-lycorane

Article abstract of DOI:10.1055/s-1993-25910

In the presence of CpCo(CO)₂, bis(trimethylsilyl)acetylene reacts with the alkyne and alkene functions of 1-(6-ethynyl-1,3-benzodioxol-5-ylcarbonyl)azacyclopent-2-ene (5c) to create CpCo-cyclohexadiene complexes embodying the polycyclic framework of γ-lycorane. A novel regioselective fluoride-mediated removal of the 2-trimethylsilyl group from these 1,2-bis(trimethylsilyl)-substituted complexes under mild conditions allowed their successful conversion into 1,12b-didehydro-7-oxo-γ-lycorane (10 steps from 6-bromo-1,3-benzodioxole-5-carboxylic acid in 9.4% overall yield). Unusual problems associated with the application of palladium catalysts in the construction of 2-functionalized alkynylarenes related to 5c were circumvented. In addition, CpCo(CO)₂ catalyzes the isomerization of the double bond of 1-acylazacyclopent-3-enes to the 2-position, but apparently is ineffective in the isomerization of N-(cyclopropylmethylidene)amines to azacyclopent-2-enes.