Dearomative enantio- and diastereoselective difluorination of resorcinol derivatives

Abstract

We herein report enantio- and diastereoselective fluorination of naphthoresorcinol and resorcinol derivatives for the first time using a dicarboxylate phase-transfer catalyst. Stereoselective oxidative transformation of resorcinol derivatives is considered to be difficult because of their high reactivity, multiple reaction sites, and multiple hydrogen bond interactions due to the presence of the two hydroxy groups. Even though resorcinol and its oxidized frameworks are widely found in bioactive natural compounds, dearomative asymmetric fluorination of resorcinol derivatives remains unexplored. We found that our chiral dicarboxylate phase-transfer catalyst could serve as an effective catalyst for the purpose. Interestingly, naphthoresorcinols and resorcinols were converted to difluorination products preferentially rather than monofluorinated products. It is noteworthy that asymmetric desymmetrization of symmetrically substituted resorcinols occurred with up to 95% ee and the reaction was tolerant of various functional groups.