Chiral Bronsted Acid Directed Iron-Catalyzed Enantioselective Friedel-Crafts Alkylation of Indoles with beta-Aryl alpha '-Hydroxy Enones

A cooperative catalytic system established by the combination of an iron salt and a chiral Bronsted acid has proven to be effective in the asymmetric Friedel-Crafts alkylation of indoles with beta-aryl alpha'-hydroxy enones. Good to excellent yields and enatioselectivities were observed for a variety of alpha'-hydroxy enones and indoles, particularly for the beta-aryl alpha'-hydroxy enones bearing an electron-with-drawing group at the para position of the phenyl ring (up to 90% yield and 91% ee). The proton of the chiral Bronsted acid, the Lewis acid activation site, as well as the inherent basic site for the hydrogen-bonding interaction of the Bronsted acid are responsible for the high catalytic activities and enantioselectivities of the title reaction. A possible reaction mechanism was proposed. The key catalytic species in the catalytic system, the phosphate salt of Fe-III, which was thought to be responsible for the high activity and good enantioselectivity, was then confirmed by ESIMS studies.