Aminoalkylation of Indoles with α-Polyfluoroalkylated Cyclic Imines

The reaction of cyclic ketimines with indoles was studied. A dramatic difference between the electrophilicity of perfluoroalkyl-substituted and non-fluorinated imines was demonstrated. In good agreement with our calculations, the Friedel-Crafts-type alkylation of indoles only takes place with alpha-polyfluoroalkylated cyclic imines that are activated by boron trifluoride-diethyl ether. The reaction proceeds under mild conditions and provides the opportunity to obtain promising alkaloid-like structures that contain a fluoroalkyl group. As a result, alpha-CF3- and alpha-C2F5-substituted pyrrolidines, piperidines, and azepanes that contain an indole moiety can be prepared efficiently.