Synthesis of (+/-)-3-Methoxyestra-1,3,5(10)-trienes by the repetitive use of Negishi reagent.

[reaction: see text] The repetitive use of Cp(2)ZrBu(2) (Negishi reagent) was applied in the synthesis of three 3-methoxyestra-1,3,5(10)-trienone isomers within four steps from the advanced intermediate 11. The overall synthesis is based on three zirconium-mediated reactions: (a) oxidative addition of a benzyl ether, (b) cyclization of an allyl-ene compound, and (c) cyclocarbonylation of a diene. The presented synthesis demonstrates that complex organic compounds can be prepared by the repetitive use of one reagent.