Totalsynthese von (–)‐Norgestrel

Total‐Synthesis of (–)‐Norgestrel (–)‐Norgestrel ( 1a ) or (–)‐norethindrone ( 1b ), two active progestational ingredients of currently used contraceptives have been synthesized stereoselectively. Compound 1a has been obtained starting from m ‐cresol methyl ether, dimethyl malonate, and ( E )‐1,4‐dibromo‐2‐butene. The steroid skeleton has been constructed using an intramolecular Diels ‐ Alder reaction of an o ‐quinodimethane derivative preceeded by a photo‐enolization of an appropriate methyl‐substituted acetophenone derivative. Chirality has been introduced at an early stage during an S cN ′ reaction (cf. Scheme 1) . Compound 1b has been obtained similarly using a previously reported mixture of the enantiomerically pure constitutional isomers 18b / 19b (cf. Scheme 3) .