A library of peralkylated bis-guanidine ligands for use in biomimetic coordination chemistry

A series of bis-guanidine ligands designed for use in biomimetic coordination chemistry has been extended to a library matrix combining unprecedented substitutional flexibility within the guanidyl residues with a wide range of aliphatic and aromatic spacers connecting these functionalities. The underlying protocol can be used with predefined ureas as well as secondary amines to build up these units by reaction with phosgene if the ureas are otherwise unavailable. In the latter case, the resulting urea intermediates do not have to be isolated as the reaction proceeds further with additional phosgene to yield a chloroformamidinium chloride which is transformed into the bis-guanidine functionality by subsequent reaction with a suitable primary diamine in the presence of triethylamine as an auxiliary base. This concept has been used to synthesise and characterise more then two dozen different bis-guanidines based on 12 discrete monoguanidine units and seven different spacers. These spacers have been chosen such that the most important phenotypes have been dealt with and which range from rigid to more flexible scaffolds. In addition to spacers with no metal-binding capabilities, other species containing further donor functions such as N-methyldiphenylenearnine or pyridine-2,6-diyl have also been used. The substitution patterns of the guanidine residues can be classified into acyclic and cyclic types. Among the cyclic types, one subset is characterised by five- or six-membered heterocycles containing both the amino nitrogen atoms and another one by individual N-heterocyclic systems for each amino nitrogen. Structurally characterised examples are 2-f-2-[2-(tetramethylguanidino)ethoxy]ethoxy)-1-(tetramethylguanidino)ethane (TMG(2)doo) in its diprotonated form and 2,2'-bis[2N-(1,1',3,3'-tetramethylguanidine)]diphenyleneamine (TMG(2)PA) as well as N-1,N-3-bis(dimorphohnomethylene)propane-1,3-diamine (DMorphG(2)P) as free bases. For the permethylated bisguanidine derivatives, the barrier to rotation around the (C=N)guanidine. bond has been determined by means of temperature-dependent EXSY H-1 NMR spectroscopy to range between 54 and 79 kJmol(-1) depending on the type of spacer. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).