Chiral Brønsted acid-catalyzed Friedel-Crafts alkylation of electron-rich arenes with in situ-generated ortho-quinone methides: highly enantioselective synthesis of diarylindolylmethanes and triarylmethanes

Abstract

We disclose herein a highly enantioselective protocol for the Brønsted acid-catalyzed addition of indoles and phenols to in situ-generated ortho-quinone methides which deliver broadly substituted diarylindolylmethanes and triarylmethanes, respectively, in a one-pot reaction under very mild conditions. A chiral phosphoric acid catalyst has been developed for this process serving to convert the starting ortho-hydroxybenzhydryl alcohols into the reactive ortho-quinone methides and to control the enantioselectivity of the carbon-carbon bond-forming event via hydrogen-bonding.