Formal total synthesis of (+/-)-estrone and zirconocene-promoted cyclization of 2-fluoro-1,7-octadienes and ru-catalyzed ring closing metathesis.

Pavel Herrmann, Milos Budesínský, Martin Kotora

Index: J. Org. Chem. 73(16) , 6202-6, (2008)

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Abstract

A new and diastereoselective method for the synthesis of the estrone skeleton from a substituted styrene based on sequential 3-fold use of Cp 2ZrBu 2 (oxidative addition-alkylation and two cyclization-alkylation sequences) and a ruthenium complex catalyzed RC-metathesis of a sterically hindered diene was developed. The prepared estratetraene was obtained in 7 steps from a commercially available starting material and thus the overall synthesis of estrone could be accomplished in 9 steps. Moreover, we have also found that the course of the reaction of substrates bearing the 2-halo-1,7-diene moiety with Cp 2ZrBu 2, i.e., cyclization or oxidative addition to the C-X bond, could be controlled by the nature of the halogen leaving group.