Enantioselective Brønsted Acid Catalysis in the Friedel-Crafts Reaction of Indoles with Secondary ortho-Hydroxybenzylic Alcohols

The reaction of indole and various methyl-substituted indoles with the title compounds was studied in the presence of chiral phosphoric acids, which act as Brønsted acid catalysts. While yields were generally high (>90%), significant enantioselectivities (up to 77% ee) were only achieved for certain substrate-catalyst combinations. In addition, a kinetic resolution of the starting material was observed, which led to an enrichment of one chiral alcohol to up to 68% ee after 76% conversion. The Friedel-Crafts reaction is not stereospecific (no direct SN2-type substitution), but rather is likely to proceed via a cation, which is bound to the chiral Brønsted acid or its anion in a close contact ion pair.