A TRAPPED INTERMEDIATE IN THE COPPER(II)-MEDIATED TEMPLATE SYNTHESIS OF AN AMINO ACID-CONTAINING LIGAND

A transition metal ion-templating reaction that has been widely exploi ted for the synthesis of nitrogen macrocycles, sepulchrates, and linea r tetradentate ligands is the template-directed Mannich condensation o f carbon acid and aldehyde equivalents with amines. In the course of i nvestigating the copper(II) template-directed synthesis of linear tetr adentate amino acid-containing ligands for the design and synthesis of double-strand DNA cleavage agents, we have trapped and characterized an intermediate in the templating reaction. Condensation of bis(phenyl alaninato)copper(II) with formaldehyde and nitroethane led to a nitro- substituent-bearing precursor complex that upon reduction is crystallo graphically characterized as enzyl-6-hydroxy-5-methyl-3-azahexanoate)c opper(II) (space group P2(1)2(1)2(1), a = 9.0066(5) Angstrom, b = 11.1 040(6) Angstrom, c = 16.009(2) Angstrom, alpha = beta = gamma = 90.0 d egrees, Z = 4, R-1 = 0.0265, wR(2) = 0.0612). NMR investigation of the precursor complex and the precursor and product ligands shows that th e templated ligands each contain only a single phenylalanine unit, not the two phenylalanine units expected on the basis of similar syntheti c procedures. The structure of the reduced product confirms this concl usion and provides structural characterization of a template intermedi ate trapped during ligand assembly.