(η6‐Arene)ruthenium(II) Labeling of Amino Acids and Peptides with Aromatic Side‐Chains

Bis(arene)ruthenium(II) complexes of the type [(η6‐cymene)Ru(η6‐aa)](CF3SO3)n (2‐9) containing L‐tyrosine and L‐tryptophan derivatives may be prepared by treatment of [(η6‐cymene)Ru({CH3)2CO}3](CF3SO3)2 with the appropriate bioligand in CH2Cl2, for fully protected compounds and CF3COOH for α‐amino acids (aa) with unprotected amine or carboxylic acid groups. Whereas the tyrosine and tryptophan methyl ester complexes [(η6‐cymene)Ru(η6‐H2tyrOMe)](CF3SO3)3 (4) and [(η6‐cymene)Ru(η6‐H2trpOMe)](CF3‐SO3)3 (8) contain trications with protonated amino functions, the remaining compounds all exhibit dications. The crystal structure analysis of [(η6‐cymene)Ru(η6‐HtyrOH)](CF3SO3)2 (5) confirms a marked distortion towards an η5‐oxohexadienyl coordination with deprotonation of the aromatic side chain. Although facial isomers are formed in an effectively 1:1 ratio for all tryptophan derivatives fractional crystallization allowed an X‐ray structural characterization of the β‐isomer of [(η6‐cymene)Ru(η6‐ActrpOMe)](CF3SO3)2 (6). Chemospecific labeling of the tryptophan side chain was established for the mixed dipeptide phenylalanyltryptophan.