Catalytic, enantioselective fluorination
Catalytic asymmetric fluorination reactions involve the formation of a carbon–fluorine bond in an enantioselective manner through the action of a nucleophilic or electrophilic source of fluorine and a chiral catalyst. While fluorinations of carbonyl compounds typically involve functionalization at the α-position, reactions of alkenes may involve the simultaneous installation of fluorine and another moiety in a vicinal relationship. Organofluorine compounds have found applications in the pharmaceutical and agrochemical industries due to their unique properties.
Unlike bromination and chlorination reactions, electrophilic fluorinations of alkenes usually do not involve the formation of a three-membered, cyclic haliranium ion. Because relatively open carbocations are involved, the scope of fluorination reactions of alkenes is limited to fairly electron-rich substrates and diminished diastereoselectivity can be observed. Reagents for electrophilic fluorination typically contain a nitrogen–fluorine bond; Selectfluor and N-fluorobenzenesulfonimide (NFSI) are prominent examples. The combination of a chiral Lewis acidic catalyst with an electrophilic fluorine source results in the enantioselective fluorination of carbonyl compounds. Likewise, chiral Lewis basic catalysts together with an electrophilic fluorine source effect the enantioselective fluorination of alkenes. Mechanisms of nucleophilic fluorination may be complicated by the varied speciation of fluoride in the presence of various metals. For example, the cobalt-catalyzed ring-opening of epoxides by fluorine proceeds through a bimetallic mechanism in which one catalyst molecule serves as a Lewis acid while the other delivers fluoride. On the other hand, palladium-catalyzed allylic fluorination reactions involve reductive elimination of an allylpalladium fluoride intermediate.