Chiral Phosphoric-Acid-Catalyzed Regioselective and Enantioselective C7-Friedel-Crafts Alkylation of 4-Aminoindoles with Trifluoromethyl Ketones

Org Lett. 2019 May 17;21(10):3538-3542. doi: 10.1021/acs.orglett.9b00821. Epub 2019 May 6.

Abstract

A highly regioselective and enantioselective C7-Friedel-Crafts alkylation of 4-aminoindoles with trifluoromethyl ketones promoted by a spirocyclic phosphoric acid was developed. This strategy was applicable to various substituted trifluoromethyl ketones and 4-aminoindole derivatives, affording the corresponding C7-functionalized indole derivatives, bearing a pharmaceutically interesting trifluoromethylated tertiary alcohol scaffold, in 21%-98% yields with up to >99% enantiomeric excess (ee).

Publication types

  • Research Support, Non-U.S. Gov't