Synthesis of orthogonally protected biaryl amino acid derivatives.
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.
Moreno
Eduardo
E
Department of Chemistry, Dainton Building, University of Sheffield, Brook Hill, Sheffield, UK S3 7HF.
Nolasco
Luca Antonio
LA
Caggiano
Lorenzo
L
Jackson
Richard F W
RF
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D010165:Palladium / Q000737:chemistry
D000596:Amino Acids; D010165:Palladium