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DOI: 10.1055/s-2007-991492
Synthesis of Estrone Methyl Ether
Contributor(s):Philip Kocienski, Indu DagerHarvard 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
Publication History
Publication Date:
18 December 2007 (online)
Key words
asymmetric reduction - oxazaborolidines -
Significance
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.
Comment
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.