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Updated: Feb 12, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Catalyst-Directed Chemoselective Double Amination of Bromo-chloro(hetero)arenes: A Synthetic Route toward Advanced
Alexandre A Mikhailine1, Gabriela A Grasa Mannino1, Thomas J Colacot1
1Johnson Matthey , 2001 Nolte Drive , West Deptford , New Jersey 098066 , United States.
Abstract:
A chemoselective sequential one-pot coupling protocol was developed for preparing several amino-anilines in high yield as building blocks for active pharmaceutical ingredients (APIs). Site (Cl vs Br on electrophile) and nucleophile (amine vs imine) selectivity is dictated by the catalyst employed. A Pd-crotyl (t-BuXPhos) precatalyst selectively coupled the Ar-Br of the polyhaloarene with benzophenone imine, even in the presence of a secondary amine, while Pd-based RuPhos or (BINAP)Pd(allyl)Cl coupled the Ar-Cl site with secondary amines.
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