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Updated: May 16, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Direct intermolecular aniline ortho-arylation via benzyne intermediates
1Department of Chemistry, University of Houston, Houston, Texas 77204-5003, USA.
Abstract:
A method for direct, transition-metal-free ortho-arylation of anilines by aryl chlorides, bromides, fluorides, and triflates has been developed. This methodology provides the most direct approach to 2-arylanilines since no protecting or directing groups on nitrogen are required. The arylation is functional-group tolerant, with alkene, ether, trifluoromethyl, dimethylamino, carbonyl, chloro, and cyano functionalities tolerated. Phenylation of enantiopure binaphthyldiamine affords a product with >99% ee.
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