Formal Total Synthesis of (±)-Estrone via the Furano Diene Approach

2011-01-07T00:00:00Z (GMT) by Ya-Ping Xue Wei-Dong Z. Li
We present in this report the development and realization of a novel formal total synthesis of estrone (<b>1</b>) via the Torgov diene (<b>24</b>) by the furano diene approach, first attempted by Woodward in 1937. The core ring structure <b>16</b> was established by an acid-mediated regioselective and stereospecific cyclization of the <i>endo</i>-oxabicyclo[2.2.1]heptene derivative <b>14</b>, which is readily available from the AlCl<sub>3</sub>-catalyzed Diels−Alder cycloaddition of 2-(3-methoxyphenethyl)furan (<b>4</b>) and dimethyl maleate. The mechanistic pathway of this S<sub>N</sub>′ type cyclization is discussed, and the earlier perspectives in our preliminary report (<i>Org. Lett.</i> <b>2004</b>, <i>6</i>, 1333) are corrected.