Origins of stereoselectivity in optically pure phenylethaniminopyridine tris-chelates M(NN′)3n+ (M = Mn, Fe, Co, Ni and Zn)

Abstract

One-pot reactions of 2-pyridinecarboxaldehyde, chiral phenylethanamines and Fe(II) give single diastereomer fac diimine complexes at thermodynamic equilibrium so that no chiral separations are required (d.r. > 200 : 1). The origins of this stereoselectivity are partly steric and partly a result of the presence of three sets of inter-ligand parallel-offset π-stacking interactions. Mn(II), Co(II), Co(III), Ni(II) and Zn(II) give similar fac structures, alongside the imidazole analogues for Fe(II). While most of the complexes are paramagnetic, the series of molecular structures allows us to assess the influence of the π-stacking present, and there is a strong correlation between this and the M-N bond length. Fe(II) is close to optimal. For the larger Zn(II) ion, very weak π-stacking leads to poorer measured stereoselectivity (NMR) but this is improved with increased solvent polarity. The mechanism of stereoselection is further investigated via DFT calculations, chiroptical spectroscopy and the use of synthetic probes.

Asymmetric triplex metallohelices with high and selective activity against cancer cells

“…The single "conventional" phenyl/pyridine -stack has a centroid-centroid distance of ca 3.60 Å, within the range we have reported previously. 28 The two -stacks between phenyl and 2,2'-bipyridine rings may be described by two such centroid-centroid distances: a shorter at 3.60-3.69 Å and a longer of 4.41-4.60 Å. The rings are close to parallel (ca 5˚) with interplanar distances of ca 3.38 Å, significantly shorter than those computed by Grimme for similar scenarios (ca 3.5 Å).…”

“…Recently we showed that by linking two diastereomerically pure tris-chelate metal complex units [28][29][30][31] via the groups X [Fig 1(d)] we could access water-compatible, stereochemically inert, functionalised helices we called flexicates. 32,33 These compounds are highly symmetrical, with the general structure of Fig1(a).…”

“…We previously established that the very high stereoselection ( v. ) in the monometallics arises largely from steric effects, while the arene -interactions shown are principally responsible for fac/mer selectivity and the unusual stability of flexicates in water. 28 Since the mer configurations cannot be present in a helicate-like structure in any event we reasoned that -stacking effects might be exploited to deliver stereoselection for the desirable, asymmetric HHT isomers of [M 2 (AB-CD) 3 ] while still retaining control over helicity. Here we report a highly stereoselective self-assembly of diverse, stable, functionalised, metallohelices with anti-parallel 'triplex' arrangement of strands.…”

Quantification of Stereochemical Communication in Metal–Organic Assemblies

“…The free energy penalty of 38 k B T for ( S )‐ b lies in the limiting regime of a large f 1  value, where the sergeant‐and‐soldiers effect is overwhelming and the chiroptical response is insensitive to the exact value (Figure S8). Between ( S )‐ c and ( S )‐ d , ( S )‐ d exhibited a stronger ability to control the configuration at the metal center, which we attribute to the greater bulk of the side group (cyclohexyl versus isopropyl) 16a, 17. We infer that both sterics and π‐stacking effects between phenyl and pyridyl rings are responsible for the strong influence of amine ( S )‐ b upon the metal‐centered configuration 16a…”

“…Remarkably, no amplification was observed for Zn II : the excess chirality of the Zn II L 3 complex 4 b increased linearly as a function of added ( S )‐ b . These observations can be understood in terms of the increased metal–ligand distance when going from Fe II through Co II to Zn II ,16a with a concomitant reduction in bond strength (see Section S5 in the Supporting Information), which in turn decreases the steric gearing of the chiral amine residues required for effective stereochemical control around the metal center.…”