Chiral Brønsted acid directed iron-catalyzed enantioselective Friedel-Crafts alkylation of indoles with beta-aryl alpha'-hydroxy enones.

Abstract

A cooperative catalytic system established by the combination of an iron salt and a chiral Brønsted 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-withdrawing group at the para position of the phenyl ring (up to 90 % yield and 91 % ee). The proton of the chiral Brønsted acid, the Lewis acid activation site, as well as the inherent basic site for the hydrogen-bonding interaction of the Brønsted 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.