Chiral Bronsted Acid Directed Iron-Catalyzed Enantioselective Friedel-Crafts Alkylation of Indoles with β-Aryl α'-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 b-aryl a’-hydroxy enones. Good to excellent yields and enatioselectivities were observed for a variety of a’-hydroxy enones and indoles, particularly for the b-aryl a’-hydroxy enones bearing an electron-withdrawing 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 FeIII, which was thought to be responsible for the high activity and good enantioselectivity, was then confirmed by ESIMS studies.