Metal coordination of the electrically neutral nitrogen atom of a tertiary carboxamide reduces the barrier to C-N-bond rotation and activates the amide towards methanolysis. X-Ray crystallographic studies indicate that this reactivity is correlated to a lifting of the amide resonance structure and concurrent pyramidalization at nitrogen. However, mechanistic data in solution have not been obtained. It became evident that structural mobility is characteristic of the complexes and the crystallographic data do not fully account for relevant reactive species. In this report we summarize IR, UV-vis, and EPR spectra of amide nitrogen coordinated bis(picolyl)amide complexes with copper(II) triflate and copper(II) chloride. A comparison between spectra sampled in the aprotic solvents dichloromethane and acetonitrile, as well as under methanolysis conditions reveals the nature of several species formed in solution. The key reactions are (I) ligand exchange involving either CH3CN or CH3OH, or, in IR experiments, bromide ions from KBr, (II) coordination-dissociation equilibria involving the urethane protecting groups of amino acid substituted ligands Boc-Xaa-bpa (Boc = tert-butoxycarbonyl, Xaa = glycine, alanine, and leucine, respectively, bpa = bis(picolyl)amine), (III) dissociation of a chloro ligand from LCuCl2 complexes and formation of square-pyramidal complex cations [LCuCl]+, and finally (IV) complete dissociation of the polydentate tertiary amide ligand to produce free copper ions in solution. Taken together, the results provide a fairly detailed qualitative picture of the processes which accompany the amide bond methanolysis.

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It is a well-established concept that the C-N bond cleavage of carboxamide functions is facilitated by the coordination of a metal ion to the carbonyl oxygen atom. In contrast, the alternative C-N bond activation by coordination of a neutral tertiary carboxamide nitrogen atom has not been studied. We present the first results on the effect of nitrogen pyramidalization in N-coordinated metal complexes on the methanolysis of tertiary carboxamide groups. An analysis of the reactions products obtained from the methanol cleavage of [(N-Acyl-bpa)Cu]2+ (bpa = N,N-bispicolylamine) complexes is presented together with experimental and high-level theoretically calculated structures. The strong effect of different anions on the amide pyramidalization and subsequent C-N-bond cleavage is evaluated. We show that dichloro complexes [(N-Acyl-bpa)CuCl2] have much less activated amide groups than the corresponding triflate species. They should therefore be less reactive. However, [(N-Acyl-bpa)CuCl2] complexes dissociate in solution to give cationic monochloro complexes [(N-Acyl-bpa)Cu(S)Cl]+ (S = solvent molecule). Theoretical calculations show that the amide pyramidalization in the monochloro complexes is equal to that in the corresponding CF3SO3- salts. Consequently, chloro and triflato complexes are cleaved with similar rates and efficiencies. Parallels to and differences in the reactivity of purely organic distorted amides are discussed.

The amino acid derived tertiary amide ligand tert-butoxycarbonyl-(S)-alanine-N,N-bis(picolyl)amide (Boc-(S)-Ala-bpa, 1) has been synthesized as a model for metal-coordinating peptide frameworks. Its reactions with copper(II) and cadmium(II) salts have been studied. Binding of Cu2+ results in amide bond cleavage and formation of [(bpa)(solvent)Cu]2+ complexes. In contrast, the stable, eight-coordinate complex [(Boc-(S)-Ala-bpa)Cd(NO3)2] (5) has been isolated and characterized by X-ray crystallography. An unusual tertiary amide nitrogen coordination is observed in 5; this gives rise to significantly reduced cis-trans isomerization barriers. Possible implications for metal-induced conformational changes in proteins are discussed.

Unusual coordination compounds: It has long been postulated that well‐known and important reactions of tertiary amides such as C‐N cleavage [Eq. (1)] and cis–trans isomerization [Eq. (2)] may proceed via nitrogen‐coordinated metal complexes. We report the first evidence for a well‐defined structure‐function relationship in these unusual compounds.