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Synthesis of Estrone Methyl EtherContributor(s):Philip Kocienski
Harvard University, Cambridge, USA
Highly Enantioselective [4+2] Cycloaddition Reactions Catalyzed by a Chiral N-Methyl-oxazaborolidinium Cation
Org. Lett. 2008, 10: 3271-3273
22 January 2009 (online)
estrone - asymmetric Diels-Alder reaction - oxazaborolidine
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.