Synthesis of Estrone Methyl Ether

Key words

estrone - asymmetric Diels-Alder reaction - oxazaborolidine

Significance

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.

Comment

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.