New route to steroidal vinyl fluorides

Abstract

Biological activity of fluorinated steroids was first discovered with 6- and 9- fluoro corticoids. Methods for the selective incorporation of fluorine into organic structures continues to be an area of growing interest for pharmaceutical research. Mechanism-based enzyme inactivation with fluorinated compounds was reported recently. In this context we were interested in steroidal vinyl fluorides for the inhibition of aromatase. We report a convenient method for the preparation of steroidal β-fluoro-α,β-unsaturated ketones e.g. 3 by reaction of the corresponding phenyl vinylsulfides e.g. 1 with N-bromosuccinimide/HF or N-bromosuccinimide/ DAST in dichloromethane. ▪ Other examples of unsaturated ketones including dienones, with yields between 50 and 70% are presented. In some cases we were able to observe and isolate intermediates of the reaction. A mechanism on the basis of these intermediates is proposed.