Brønsted acid catalyzed monoalkylation of anilines with trichloroacetimidates

J Org Chem. 2015 Feb 6;80(3):1993-2000. doi: 10.1021/jo5027222. Epub 2015 Jan 16.

Abstract

Trichloroacetimidates are useful alkylating agents for aromatic amines, requiring only a catalytic amount of a Brønsted acid to facilitate the reaction. Monoalkylation predominates under these conditions. Electron-poor anilines provide superior yields, with electron-rich anilines sometimes showing competitive Friedel-Crafts alkylation. A single flask protocol with formation of the imidate in situ is demonstrated, providing a convenient method for the direct substitution of alcohols with anilines. Reaction with a chiral imidate favors a mechanism that proceeds through a carbocation intermediate.