Enantioselective electrophilic fluorination of α-aryl-α-tetralones

Several bioactive chiral compounds bearing stereogenic centers at the α-position of carbonyl groups with one enolizable hydrogen, can suffer epimerization under physiological conditions.[1] To avoid that, hydrogen atom can be replaced by fluorine. This replacement in bioactive compounds promotes changes in the stability, lipophilicity and reactivity, without increasing steric requirements.[2,3] In this work, we developed an enantioselective α-fluorination of o-substituted α-aryl-α-tetralones using ammonium salts of Cinchona alkaloids.We have screened different combination of in situN-fluoroammonium salts of Cinchone alkaloid derivatives in various temperatures for the enantioselective electrophilic fluorination of α-aryl-α-tetralones using as model, α-(2-methoxyphenyl)-tetralone. The enantioselectivity in this reaction showed a strong dependence of the substituent in C ring for electron donor o-substituent. Although moderately efficient from the point of view of enantioselectivity (up to 70% ee), our experiments showed a significant difference between cinchone derivatives, the influence of the substrate and the temperature in these kind of reaction.