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Updated: Jul 19, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Synthesis of orthogonally protected biaryl amino acid derivatives
Eduardo Moreno1, Luca Antonio Nolasco, Lorenzo Caggiano
1Department of Chemistry, Dainton Building, University of Sheffield, Brook Hill, Sheffield, UK S3 7HF.
Abstract:
The efficient and direct synthesis of protected biaryl amino acids, including dityrosine (50% overall yield over 3 steps), by Negishi cross-coupling of the serine-derived organozinc reagent 4 with iodo- and di-iodobiaryls, is reported. An improved, although still not perfect, diiodination of 2,2'-biphenol has been achieved using NMe3BnICl2-ZnCl2. Protection of phenolic hydroxyl groups as acetates, rather than benzyl ethers, is required for efficient cross-coupling, and evidence for acetyl migration has been observed during debenzylation of a substituted 2-acetoxy-2'-benzyloxybiaryl. Aromatic C-I to C-Cl conversion has been detected as a minor reaction pathway in the palladium-catalyzed coupling of aryl iodide 3b with organozinc reagent 4.
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