Enolate Stabilization by Anion–π Interactions: Deuterium Exchange in Malonate Dilactones on π‐Acidic Surfaces

Of central importance in chemistry and biology, enolate chemistry is an attractive topic to elaborate on possible contributions of anion- interactions to catalysis. To demonstrate the existence of such contributions, experimental evidence for the stabilization of not only anions but also anionic intermediates and transition states on -acidic aromatic surfaces is decisive. To tackle this challenge for enolate chemistry with maximal precision and minimal uncertainty, malonate dilactones are covalently positioned on the -acidic surface of naphthalenediimides (NDIs). Their presence is directly visible in the upfield shifts of the -protons in the (HNMR)-H-1 spectra. The reactivity of these protons on -acidic surfaces is measured by hydrogen-deuterium (H-D) exchange for 11 different examples, excluding controls. The velocity of H-D exchange increases with acidity (NDI core substituents: SO2R>SOR>H>OR>OR/NR2>SR>NR2). The H-D exchange kinetics vary with the structure of the enolate (malonates>methylmalonates, dilactones>dithiolactones). Moreover, they depend on the distance to the surface (bridge length: 11-13 atoms). Most importantly, H-D exchange depends strongly on the chirality of the surface (chiral sulfoxides as core substituents; the crystal structure of the enantiopure (R,R,P)-macrocycle is reported). For maximal acidity, transition-state stabilizations up to -18.8kJmol(-1) are obtained for H-D exchange. The BrOnsted acidity of the enols increases strongly with acidity of the aromatic surface, the lowest measured pK(a)=10.9 calculates to a pK(a)=-5.5. Corresponding to the deprotonation of arginine residues in neutral water, considered as impossible in biology, the found enolate- interactions are very important. The strong dependence of enolate stabilization on the unprecedented seven-component -acidity gradient over almost 1eV demonstrates quantitatively that such important anion- activities can be expected only from strong enough acids.