Catalytic Asymmetric Synthesis of 3‑Hydroxy-3-trifluoromethyl Benzofuranones via Tandem Friedel–Crafts/Lactonization Reaction

Abstract

A highly enantioselective and regioselective chiral Lewis acid catalyzed tandem Friedel–Crafts/lactonization reaction is reported, providing direct access to plenty of 3-hydroxy-3-trifluoromethyl benzofuran-2-ones in up to 94% yields with up to >99% ee. Mechanistic study reveals that the interactions between the phenolic hydroxyl group and trifluoropyruvate are the most likely contributing factor to the high enantio- and regioselectivity. Optically pure (−)-BHFF can be obtained in gram-scale with 0.05 mol % catalyst, demonstrating the potentially utility of this method in medicinal chemistry