Fluorination of steroid estrogens with Selectfluor ® : Elucidation of regio- and stereoselectivity

Synthesis, Biological Evaluation and Docking Studies of 13-Epimeric 10-fluoro- and 10-Chloroestra-1,4-dien-3-ones as Potential Aromatase Inhibitors

“…When fluorinations were carried out at 80 °C in acetonitrile, the same 10-fluoro products ( 9 or 17 ) were formed, but the reaction was complete within 1 h (Table 1, Entries 2 and 8). Our results are not consistent with those obtained for monosubstituted phenols [13], but they show good correspondence with chemoselectivities obtained earlier for fluorinations of estrone derivatives with Selectfluor [14,15,16,17]. In methanol, however, ortho-fluorinations also occurred (15–16%: 15 : 16 =1:0.9 or 18 : 19 =1:1.5) at both reaction temperatures (Table 1, Entries 4,5,10 and 11).…”

“…According to the literature, 17β-estradiol ( 6 ), estrone ( 7 ) or their certain ring D-substituted derivatives can be converted to 10β-fluoroestra-1,4-dien-3-one analogues ( 8 and 9 ) with Selectfluor in different solvents (acetonitrile or bmimBF 4 :MeOH = 1:1, H 2 O) or under solvent-free conditions (Scheme 2) [14,15,16,17]. Independent of the nature of the solvent, all reactions resulted in dienones 8 and 9 as main products.…”

“…ortho -substituted derivatives were observed only in trace amounts. Bogautdinov et al reported the stereoselective fluorination of the 8α-epimer of 17β-estradiol ( 10 ) in the 1:1 mixture of bmimBF 4 and methanol (Scheme 2) [14]. They proved that the reaction leads to 10-fluoro derivative 11 as the main product with α-orientation of fluorine.…”