Synfacts 2009(2): 0117-0117  
DOI: 10.1055/s-0028-1087603
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Estrone Methyl Ether

Rezensent(en):Philip Kocienski
E. Canales, E. J. Corey*
Harvard University, Cambridge, USA
Highly Enantioselective [4+2] Cycloaddition Reactions Catalyzed by a Chiral N-Methyl-oxazaborolidinium Cation
Org. Lett.  2008,  10:  3271-3273  
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22. Januar 2009 (online)


Canales and Corey report a ­remarkably short and efficient synthesis of estrone methyl ether which exploits a novel N-methyl­oxazaborolidinium cation as a Lewis acid catalyst for an asymmetric Diels-Alder reaction. The paper cites ten further examples all proceeding with excellent yields and ee values. The reactions typically proceed in dichloromethane at -78 ˚C but in the estrone synthesis depicted, the cycloaddition was performed at room temperature. The ee of the adduct D (82%) was raised to 99% by one recrystallization.


The highly reactive catalyst C was generated in situ prior to use. It could not be generated by N-methylation of the corresponding ­oxazaborolidine; nor could it be generated by the reaction of N-methyl-1,1-diphenyl-pyrrolidino­methanol or the corresponding bistrimethylsilyl ether with ArBBr2 or ArB(OTf)2. For a related synthesis of estrone methyl ether see: Y.-Y. Yeung, R.-J. Chein, J. E. Corey J. Am. Chem. Soc. 2007, 129, 10346.