CATION-STABILIZING AUXILIARIES IN POLYENE CYCLIZATIONS .5. THE FLUORINE ATOM AS A CATION-STABILIZING AUXILIARY IN BIOMIMETIC POLYENE CYCLIZATIONS .2. ASYMMETRIC-SYNTHESIS OF A STEROID

The use of the fluorine atom as a cation-stabilizing (C-S) auxiliary for enhancing polyene cyclizations has been improved in synthetic effectiveness by the demonstration that the dl acetal 5 can be converted to the racemic fluorocycle 6, bearing the natural backbone configuration of the steroids. Cyclization of enantiopure S,S acetal 5a afforded the fluorocycle 6a in 38% yield with 93% ee. Retention of the fluorine atom in the tetracycle allowed for the smooth reduction of 6a, using the Ohsawa-Oishi reagent, to compound 22a, in which the fluorine atom is replaced stereoselectively by hydrogen, with retention of configuration, as shown by the conversion of 22a to the known steroid 4beta-hydroxyandrostan-17-one (27a). Five compounds make up the relatively high-yielding (69-83%) tetracyclic portion of the cyclization product mixture, affording the possibility that further structural modifications of the cyclization substrate bearing the pro-C-8 fluoro group as a C-S auxiliary will lead to practical synthetic routes to fluorosteroids and triterpenoids. In the next two papers in this series, this potential is demonstrated further by the synthesis of beta-amyrin.