2022 Volume 80 Issue 7 Pages 632-644
Introduction of fluorine atom(s) into an organic framework is one of the common strategies in life science field due to its unique properties. Therefore, fluorine atom(s) can be found in many bioactive compounds including medicinal drugs. Considering chiral environment in nature, the development of efficient fluorination to construct chiral fluorine-containing compounds is an important subject. In this context, we have studied the development of asymmetric fluorofunctionalization of alkenes and deraomative fluorination of aromatic compounds using a newly designed phase-transfer catalysts. In 2015, we reported the first successful example of asymmetric fluorolactonization using a hydroxy-carboxylate catalyst. Based on the mechanistic studies of the fluorolactonization, we were able to create a dianionic phase-transfer catalyst with more efficient catalytic activity. The dianionic phase-transfer catalyst was found to promote asymmetric 6-endo-fluorocyclization and deprotonative fluorination of simple cyclic and acyclic allylic amides, asymmetric fluorocyclization of ene-oximes, and dearomatizing fluorinations of indoles, 2-naphthols, and resorcinols. According to the mechanistic studies using allylic amides, the active catalytic species switches depending on the substitution pattern of allylic amides, which would result in the reversal of the face-selectivity. Thus, an active aggregate of the catalyst/Selectfluor ion pair promotes the reaction of γ,γ-disubstituted allylic amides, while a monomer complex would be active for γ-monosubstituted substrates.
