Enantioselective Friedel-Crafts Alkylation Reaction of Heteroarenes with N-Unprotected Trifluoromethyl Ketimines by Means of Chiral Phosphoric Acid

Abstract

An enantioselective Friedel-Crafts alkylation reaction of pyrroles and indoles with N-unprotected trifluoromethyl ketimines by use of chiral phosphoric acid provided α-trifluoromethylated primary amines bearing chiral tetrasubstituted carbon centers in high yields and with high to excellent enantioselectivities. The present reaction is unique to N-unprotected trifluoromethyl ketimines. No reaction took place with N-p-methoxyphenyl (PMP)-substituted ketimine. Corresponding α-trifluoromethylated amines were transformed without loss of enantioselectivity.

Keywords: chiral phosphoric acid; indoles; nucleophilic addition; pyrroles; trifluoromethyl ketimine.