Synergistic Anion–(π)_n–π Catalysis on π-Stacked Foldamers

Abstract

In this report, we demonstrate that synergistic effects between π-π stacking and anion-π interactions in π-stacked foldamers provide access to unprecedented catalytic activity. To elaborate on anion-(π) -π catalysis, we have designed, synthesized and evaluated a series of novel covalent oligomers with up to four face-to-face stacked naphthalenediimides (NDIs). NMR analysis including DOSY confirms folding into π stacks, cyclic voltammetry, steady-state and transient absorption spectroscopy the electronic communication within the π stacks. Catalytic activity, assessed by chemoselective catalysis of the intrinsically disfavored but biologically relevant addition reaction of malonate half thioesters to enolate acceptors, increases linearly with the length of the stacks to reach values that are otherwise beyond reach. This linear increase violates the sublinear power laws of oligomer chemistry. The comparison of catalytic activity with ratiometric changes in absorption and decreasing energy of the LUMO thus results in superlinearity, that is synergistic amplification of anion-π catalysis by remote control over the entire stack. In computational models, increasing length of the π-stacked foldamers correlates sublinearly with changes in surface potentials, chloride binding energies, and the distances between chloride and π surface and within the π stack. Computational evidence is presented that the selective acceleration of disfavored but relevant enolate chemistry by anion-π catalysis indeed originates from the discrimination of planar and bent tautomers with delocalized and localized charges, respectively, on π-acidic surfaces. Computed binding energies of keto and enol intermediates of the addition reaction as well as their difference increase with increasing length of the π stack and thus reflect experimental trends correctly. These results demonstrate that anion-(π)-π interactions exist and matter, ready for use as a unique new tool in catalysis and beyond.

Remote Control of Anion–π Catalysis on Fullerene‐Centered Catalytic Triads

“…This activity is outstanding not only in the context of this work, it is a new record for anion–π interactions in organocatalysis (excluding anion–π enzymes) 3, 4, 5, 7. The activity found for triad 1 exceeded expectations from the lowering LUMO levels of fullerenes from 6 to 2 and 1 clearly (Figures 3 e,f) and disagreed with predictions based on π holes on the central fullerene (Figures 3 e,g).…”

“…Their comparable relevance is generally recognized only if the interactions are too strong and continue into either nucleophilic and electrophilic aromatic substitutions or the generation of radical anions and cations, respectively. Whereas the exact nature of anion–π interactions is still under debate, intrinsic π acidity, that is, low‐lying LUMO energies, π holes (areas with positive molecular electrostatic potential (MEP), Figures 1 a,b), positive quadrupole moments perpendicular to the aromatic plane or in‐plane dipoles from electron‐withdrawing substituents, have received much attention, resulting in much interest in small, compact π surfaces such as, for instance, in hexafluorobenzene or naphthalenediimides (NDIs) 1, 3, 4, 5. Despite much encouragement from pioneering theoretical studies,6 induced anion–π interactions have been largely ignored in practice.…”

“…Despite much encouragement from pioneering theoretical studies,6 induced anion–π interactions have been largely ignored in practice. However, very recent results from anion–π catalysis, that is, the stabilization of anionic transition states on aromatic surfaces,3 revealed that activities increase in response to electric fields,4 with increasing length of π‐stacked foldamers,5 and on fullerenes 7. The discovery of anion–π catalysis on fullerenes was of particular interest because this most popular carbon allotrope8 has received little attention with regard to both anion–π interactions9 and catalysis 10.…”

“…The addition of malonic acid half thioester (MAHT) 17 to nitroolefin 18 was selected to probe anion–π catalysis with triads 1 – 5 (Figure 3 a) 3, 4, 5. This transformation has emerged as the benchmark reaction.…”

“…Anion-p interactions [1] refer to the attraction between anions and aromatic surfaces.T his is opposite to the conventional cation-p interaction [2] between ap ositive charge and a p-basic aromatic surface,and much less recognized because it is counterintuitive.Their comparable relevance is generally recognized only if the interactions are too strong and continue into either nucleophilic and electrophilic aromatic substitutions or the generation of radical anions and cations, respectively.W hereas the exact nature of anion-p interactions is still under debate,intrinsic p acidity,that is,low-lying LUMO energies, p holes (areas with positive molecular electrostatic potential (MEP), Figures 1a,b), positive quadrupole moments perpendicular to the aromatic plane or inplane dipoles from electron-withdrawing substituents,h ave received much attention, resulting in much interest in small, compact p surfaces such as,f or instance,i nh exafluorobenzene or naphthalenediimides (NDIs). [1,[3][4][5] Despite much encouragement from pioneering theoretical studies, [6] induced anion-p interactions have been largely ignored in practice.However,very recent results from anion-p catalysis, that is,t he stabilization of anionic transition states on aromatic surfaces, [3] revealed that activities increase in response to electric fields, [4] with increasing length of pstacked foldamers, [5] and on fullerenes. [7] Thed iscovery of anion-p catalysis on fullerenes was of particular interest because this most popular carbon allotrope [8] has received little attention with regard to both anion-p interactions [9] and catalysis.…”