Organocatalytic Friedel-Crafts Alkylation/Lactonization Reaction of Naphthols with 3-Trifluoroethylidene Oxindoles: The Asymmetric Synthesis of Dihydrocoumarins

Abstract

Naphthols and 3-trifluoroethylidene oxindoles were found to undergo an asymmetric Friedel-Crafts alkylation/lactonization reaction, catalyzed by only 2.5 mol % of a quinine-derived squaramide catalyst, to afford the corresponding α-aryl-β-trifluoromethyl dihydrocoumarin derivatives in high yields (up to 99 %) with excellent enantio- and diastereoselectivities (up to 98 % ee, >20:1 d.r.). Importantly, the lactonization proceeded by nucleophilic attack of the naphthol hydroxy group at the amide motif of the oxindoles under mild reaction conditions. This protocol represents a new strategy for the formation of dihydrocoumarins by an efficient intramolecular amide C-N bond-cleavage and esterification process.

Keywords: amides; arenes; heterocycles; organocatalysis; synthetic methods.