Enantioselective Friedel-Crafts Alkylation Reaction of Pyrroles with N-Unprotected Alkynyl Trifluoromethyl Ketimines

Developed herein is an enantioselective Friedel-Crafts alkylation reaction of N-unprotected alkynyl trifluoromethyl ketimines with pyrroles catalyzed by chiral phosphoric acid to furnish chiral primary alpha-trifluoromethyl-alpha-(2-pyrrolyl)propargyl-amines with high enantioselectivity. Transformation of the alkynyl group of the adducts afforded optically active alpha-trifluoromethylated amines bearing various substituents such as alkyl, alkenyl, enyne, and triazole without loss of optical purity.

Automated summary

In this study, an enantioselective Friedel-Crafts alkylation reaction was developed using chiral phosphoric acid as the catalyst to react N-unprotected alkynyl trifluoromethyl ketimines with pyrroles, resulting in the synthesis of chiral primary alpha-trifluoromethyl-alpha-(2-pyrrolyl)propargyl-amines with high enantioselectivity. The alkynyl group of the adducts can be transformed without a loss of optical purity, leading to optically active alpha-trifluoromethylated amines bearing various substituents.