Electrophilic fluorination of some steroidal α,β-unsaturated ketones

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Abstract
3β-Acetoxy-5α,6β-dichloropregn-16-en-20-one (1), on treatment with elemental fluorine at low temperature, gave the 16α,17α-difluoro-adduct (2) and, by rearrangement, the 13α,16α-difluoro-17β-methyl derivative (3). The adduct (2) was subsequently converted via a short, efficient synthetic sequence into 16α,17α-difluoroprogesterone (5). In contrast, fluorination of 21-acetoxypregna-1,4,16-triene-3,11,20-trione (6) afforded the corresponding 16α,17α-difluoro-adduct (8) in low yield. Similarly, androsta-1,4,6-triene-3,17-dione (9) was converted into the 6α,7α-difluoro-adduct (11). Fluorination with CF3OF led to an increased yield of the adduct (11) and also afforded the 6α-trifluoromethoxy-7α-fluoro-adduct (12). Dehydrofluorination of the latter gave 6-trifluoromethoxyandrosta-1,4,6-triene-3,17-dione (13). 21-Acetoxy-11β,17α-dihydroxypregna-1,4,6-triene-3,20-dione (5) was prepared by stepwise dehydrogenation of cortisol acetate (14). Subsequent low temperature treatment with CF3OF resulted in two major products, formulated as the adducts (17) and (18).