Synthesis of Estrone Methyl Ether

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.