Anion-π Catalysis

The introduction of new noncovalent interactions to build functional systems is of fundamental importance. We here report experimental and theoretical evidence that anion-pi interactions can contribute to catalysis. The Kemp elimination is used as a classical tool to discover conceptually innovative catalysts for reactions with anionic transition states. For anion-pi catalysis, a carboxylate base and a solubilizer are covalently attached to the pi-acidic surface of naphthalenedfimides. On these pi-acidic surfaces, transition-state stabilizations up to Delta Delta G(TS) = 31.8 +/- 0.4 kJ mol(-1) are found. This value corresponds to a transition-state recognition of K-TS = 2.7 +/- 0.5 mu M and a catalytic proficiency of 3.8 x 10(5) M-1. Significantly increasing transition-state stabilization with increasing pi-acidity of the catalyst, observed for two separate series, demonstrates the existence of "anion-pi catalysis." In sharp contrast, increasing if-acidity of the best naphthalenediimide catalysts does not influence the more than 12000-times weaker substrate recognition (K-M = 34.5 +/- 1.6 mu M). Together with the disappearance of Michaelis-Menten kinetics on the expanded pi-surfaces of perylenediimides, this finding supports that contributions from pi-pi interactions are not very important for anion-pi catalysis. The linker between the pi-acidic surface and the carboxylate base strongly influences activity. Insufficient length and flexibility cause incompatibility with saturation kinetics. Moreover, preorganizing linkers do not improve catalysis much, suggesting that the ideal positioning of the carboxylate base on the pi-acidic surface is achieved by intramolecular anion-pi interactions rather than by an optimized structure of the linker. Computational simulations are in excellent agreement with experimental results. They confirm, inter alia, that the stabilization of the anionic transition states (but not the neutral ground states) increases with the pi-acidity of the catalysts, i.e., the existence of anion-pi catalysis. Preliminary results on the general significance of anion-pi catalysis beyond the Kemp elimination are briefly discussed.