Formal total synthesis of (+/-)-estrone and zirconocene-promoted cyclization of 2-fluoro-1,7-octadienes and ru-catalyzed ring closing metathesis.
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.
Herrmann
Pavel
P
Department of Organic and Nuclear Chemistry, and Centre for New Antivirals and Antineoplastics, Faculty of Science, Charles University, Hlavova 8, 128 43 Praha 2, Czech Republic.
Budesínský
Milos
M
Kotora
Martin
M
D000466:Alkadienes / Q000737:chemistry*; D000478:Alkylation; D002384:Catalysis; D003500:Cyclization; D004970:Estrone / Q000138:chemical synthesis* / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry; D013237:Stereoisomerism; D013343:Styrenes / Q000737:chemistry; D015040:Zirconium / Q000737:chemistry*
D000466:Alkadienes; D009942:Organometallic Compounds; D013343:Styrenes; C023398:Zirconocene dichloride; D004970:Estrone; D012428:Ruthenium; D015040:Zirconium