A unified strategy for iron-catalyzed ortho-alkylation of carboxamides
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Updated: Apr 26, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Erin R Fruchey1, Brendan M Monks, Silas P Cook
1Department of Chemistry, Indiana University , 800 East Kirkwood Avenue, Bloomington, Indiana 47405-7102, United States.
Abstract:
Using 8-aminoquinoline-based aryl carboxamides, the direct ortho-alkylation can be achieved in high yields in the presence of an iron source, 1,2-bis(diphenylphosphino)ethane (dppe) and phenylmagnesium bromide. The reactions proceed without overalkylation and provide high levels of regioselectivity. The benzylation reactions can be performed in air with reagent-grade THF, while the alkylation works well with unactivated secondary bromides and iodides in 2-methyltetrahydrofuran. Moreover, the reactions only require 5-10 min.
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