Complexes of 5,5 '-aminoacido-substituted 2,2 '-bipyridyl ligands: control of diastereoselectivity with a pH switch and a chloride-responsive combinatorial library

The synthesis and coordination chemistry of a new chiral ligand, 2,2'-bipyridine substituted at the 5 and 5' positions by N-methyl-L-valine methyl ester (5), is presented. The ligand readily forms complexes [M(5)(3)](2+) where M=Co(II) and Fe(II) in CH3CN, and the complexation reaction is slightly diastereoselective (d.e.=ca. 20%) in favour of the Delta diastereomer. The addition of six equivalents of HCl to these complexes [M-II(5)(3)](2+) leads to formation of Delta-[M-II(5H(2))(3)](8+) with a d.e. of 100%. This high diastereoselectivity can be reversed by the addition of base i.e. the diastereoselectivity can be controlled by the pH. Delta-[Fe(5H(2))(3)](8+) was found to bind chloride ions in CD3OD-CD3CN (6:1) with a binding constant of 260 M-1. [Co-II(5)(3)](2+) can be oxidised to Delta-[Co-III(5H(2))(3)](9+). Formation constants for both [Co-II(5)(3)](2+) and [Co-II(5H(2))(3)](8+) in acetonitrile were obtained by spectrophotometric titrations. In the former case, the stability constant, log beta(3)=19.5(8), is very similar to that measured for [Co-II(bipy)(3)](2+) (log beta(3)=19.3(7)) but this drops significantly when the amine groups of 5 are protonated (log beta(3)=16.5(2)). A dynamic combinatorial library was prepared by mixing three equivalents of 5, three equivalents of bipy, and two equivalents of Co(II) in CD3CN. The presence of all possible Delta- and Lambda-[Co-II(5)(x)(bipy)(3-x)](2+) complexes was inferred from H-1 NMR and ES-MS spectra. Addition of protons to this library reduced the number of components by inducing diastereoselectivity, and presence of chloride further simplified the H-1 NMR spectrum, indicating that {Cl(2)subset ofDelta-[Co-II(5H(2))(3)]}(6+) and [Co-II(bipy)(3)](2+) were the dominant products.