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

Abstract

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 Δ diastereomer. The addition of six equivalents of HCl to these complexes [M^II(5)₃]²⁺ leads to formation of Δ-[M^II(5H₂)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. Δ-[Fe(5H₂)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 Δ-[Co^III(5H₂)₃]⁹⁺. Formation constants for both [Co^II(5)₃]²⁺ and [Co^II(5H₂)₃]⁸⁺ in acetonitrile were obtained by spectrophotometric titrations. In the former case, the stability constant, logβ₃ = 19.5(8), is very similar to that measured for [Co^II(bipy)₃]²⁺ (logβ₃ = 19.3(7)) but this drops significantly when the amine groups of 5 are protonated (logβ₃ = 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 Δ- and Λ-[Co^II(5)_x(bipy)_3−x]²⁺ complexes was inferred from ¹H 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 ¹H NMR spectrum, indicating that {Cl₂⊂Δ-[Co^II(5H₂)₃]}⁶⁺ and [Co^II(bipy)₃]²⁺ were the dominant products.