A novel one-flask cyclopentannulation involving a dilithiomethane equivalent as a β-connector of two enones. A highly efficient total synthesis of (±)-hirsutene

Article abstract of DOI:10.1016/S0040-4020(01)88017-0

Five- and six-membered rings can be constructed in one flask from two different enones and tris(phenylthio)methyllithium. The latter behaves as a dilithiomethane equivalent when its central carbon atom adds in conjugate fashion to one enone, becomes nucleophilic again when one of its phenylthio groups is exchanged for lithium in the presence of sec-butyllithium, and then undergoes conjugate addition to a second enone to provide a dienolate dianion. The latter can be oxidized to a 1,4-diketone incorporating a cyclopentane ring or induced to undergo an aldol reaction to produce a six-membered ring. In some of the cases, an interesting stereochemical equilibration occurs during the oxidation leading to one of two possible diastereomers and the overall process results in a highly efficient, stereospecific synthesis of (±)-hirsutene 13.