20-Fluoro-17 -pregnenolone

The addition of HF to the 5,6-double bond in 3-hydroxy-A -steroids has been investigated intensively. Bowers et al. prepared the 5oc-fluoro derivative (32) from pregnenolone acetate (31) in 10 % yield using methylene dichloride-THF as solvent at 0°. Pregnenolone itself is converted in 30%... 

The scheme required to prepare the potent tri-fluoro corticoid cormethasone acetate (292) illustrates the synthetic complexities involved in some of this work. Sequential acetylation of the pregnenolone derivative 278 with first acetic anhydride in pyridine and then acetic anhydride in the presence of tosic acid affords diacetate 279. Reaction of that intermediate with nitrosyl fluoride results initially in addition of the reagent to the 5,6-olefin moiety to afford the fluoro oxime reaction with a second mole of reagent at nitrogen gives the nitroimine derivative 280 passage over alumina serves to hydrolyze the imine function to the corresponding 6-ketone (281). 

Pregnenolone undergoes addition of iodine fluoride to give 5a-fluoro-3 -hydroxy-6jS-iodopreg-nan-20-one (4). ... 

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