Synthesis of Estrone Methyl Ether

doi:10.1055/s-2007-991492

Synfacts 2008(1): 0003-0003
DOI: 10.1055/s-2007-991492

Synthesis of Natural Products and Potential Drugs

Synthesis of Estrone Methyl Ether

Contributor(s):Philip Kocienski, Indu Dager

Y.-Y. Yeung, R. J. Chein, E. J. Corey*
Harvard University, Cambridge, USA
Conversion of Torgov’s Synthesis of Estrone into a Highly Enantioselective and Efficient Process
J. Am. Chem. Soc. 2007, 129: 10346-10347

Abstract

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Key words

asymmetric reduction - oxazaborolidines -

Significance

<P>The short and efficient synthesis of estrone methyl ether reported here is a modified enantioselective version of the Torgov and Ananchenko synthesis (Tetrahedron Lett. 1963, 4, 1553). Although the key step in the synthesis involved an oxazaborolidine D, the reaction proceeded by a different pathway from the CBS reduction, via transition state I where the catecholborane-PhNEt₂ complex was a hydride donor rather than the oxazaborolidine-catecholborane complex. This method provides a practical alternative to the use of enzymes for reducing cyclic 1,3-diketones.</P>

Comment

<P>Reduction of ketone C proceeded with high stereoselectivity via transition state I and a single recrystallization afforded E in 99% ee. A similar reduction methodology was applied to five other cyclic 1,3-diketones with excellent enantioselectivity. Acidic treatment of alcohol E followed by oxidation and then reduction gave estrone methyl ether in good overall yield.</P>

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