Binary Acid Catalysis in Enantioselective Friedel-Crafts Reactions

Significance

Even though a number of chiral acid catalysts were developed for asymmetric Friedel-Crafts reaction involving activated substrates, for example pyrroles and indoles, only ­limited success was achieved with less active compounds, such as phenols. In this paper the authors design a catalytic system consisting of a Brønsted and a Lewis acid, which was expected to show enhanced acidity according to Yamamoto’s combined acid principles. Thus, MgF₂ was found to be a uniquely efficient additive to chiral phosphoric acid 1 to construct a highly enantioselective catalytic system for alkylation of phenols by β,γ-unsaturated α-keto esters. The developed system also demonstrated high performance when indoles were used as substrates.