Electric Field-Induced Anion-π Catalysis on Carbon Nanotubes in Electrochemical Microfluidic Reactors

Oriented external electric fields (OEEFs) have long tantalized researchers as a theoretical means to accelerate and direct the flow of charges during molecular transformations. The idea behind OEEFs is to exploit the influence of external electric fields on chemical reactions, which can open doors to a wide range of applications. These include accelerating chemical reactions, enabling diverse reactivities, and providing insights into mimicking enzyme function. However, despite extensive efforts and promising individual achievements, practical progress in leveraging OEEFs for organic synthesis has been limited. In a recent study published in the Journal Science Advances, a team of researchers led by M. Ángeles Gutiérrez López, Rojan Ali, Mei-Ling Tan, Naomi Sakai, Thomas Wirth, and Stefan Matile from the University of Geneva focused on the utilization of OEEFs to catalyze chemical reactions, a concept that has long held promise in theory but remained challenging to implement practically.  Their study demonstrated the feasibility of anion-π catalysis, and by implication, cation-π catalysis, on carbon nanotubes within electrochemical microfluidic reactors, offering a robust platform for electric field-induced catalysis under experimentally relevant conditions.

The research team method combines essential principles from different domains, emphasizing the use of electrochemical microfluidic reactors. These reactors have gained prominence in recent years for their ability to maximize the utility of electrochemical redox reactions, particularly in industrial and environmental contexts. The key advantage of electrochemical microfluidic reactors lies in their capability to generate strong electric fields at low voltages without triggering electron transfer, thereby circumventing the major challenge associated with OEEFs. Moreover, the close proximity of electrodes in these microfluidic reactors offers intrinsic conductivity, eliminating the need for additional electrolytes. This is particularly advantageous for anion-π and cation-π catalysis within OEEFs. Additionally, the high surface-to-volume ratio in these reactors enables operational catalysis at high substrate concentrations, while the directional flow minimizes the risk of product inhibition.

Central to the success of the new approach is the utilization of multiwalled carbon nanotubes (MWCNTs) as catalytic platforms. MWCNTs, composed of single-walled carbon nanotubes wrapped around each other, possess exceptional polarizability due to their extended aromatic systems. Importantly, MWCNTs can facilitate electron relocation in response to charged molecules and OEEFs, both along and between the stacked aromatic systems. This intra- and intertube electron relocation effectively transforms OEEFs into giant oriented macrodipoles, generating strong local electric fields capable of catalyzing reactions even at low external voltages below the onset of electron transfer. The orientation of these giant macrodipoles in response to the applied OEEF interacts directionally with anionic and cationic parts of reactive intermediates and transition states, facilitating and directing the flow of electrons during the reaction. Consequently, this leads to anion-π and cation-π catalysis, offering a powerful means to accelerate and control charge movement during chemical transformations. Given that localized charge displacement is a common feature in most reactions, electric field-induced anion/cation-π catalysis on MWCNTs emerges as a promising tool for organic synthesis.

The authors primarily focused on anion-π catalysis due to its relatively less explored nature in comparison to cation-π interactions. Anion-π catalysis involves the stabilization of anionic transition states on π-acidic aromatic surfaces, and its potential in catalysis has gained attention in recent years. Notably, anion-π interactions on larger aromatic systems with high polarizability, such as MWCNTs, have emerged as particularly effective for catalysis. Catalysis on carbon nanotubes and related carbon allotropes, including graphene and graphite, has been the subject of extensive investigation. While these materials have been used as scaffolds or redox partners in previous studies, their explicit application in anion-π or cation-π catalysis was largely unexplored until this recent research. The researchers marked a significant departure from convention, offering a novel approach to catalysis by harnessing the unique properties of MWCNTs.

The key catalytic reactions investigated in their study revolve around epoxide-opening ether cyclizations on π-acidic surfaces. These reactions are particularly intriguing because they do not require additional activating groups and exhibit autocatalytic behavior, even in the absence of directing methyl groups. The study employed these epoxide-opening ether cyclizations as benchmark reactions to elucidate electric field-induced anion-π catalysis on carbon nanotubes within electrochemical microfluidic reactors.

The researchers found that in suspension, MWCNTs alone did not substantially catalyze the conversion of substrates. To address this challenge, the researchers designed substrates with interfacing moieties, allowing them to form formal substrate-catalyst complexes. The role of these interfacing moieties, such as pyrene, was critical in ensuring efficient binding of substrates to MWCNTs, resulting in the formation of stable complexes that facilitated rapid substrate conversion. They also demonstrated that the presence of MWCNTs in suspension led to substantial rate enhancements in substrate conversion, with higher concentrations of MWCNTs yielding greater enhancements. This observation validated the concept of anion-π catalysis on suspended MWCNTs and highlighted the significance of interfacers in bringing substrates and catalysts into close proximity. Furthermore, they explored inhibition and autocatalysis effects. The addition of inhibitors or product analogs revealed that the presence of these molecules could decelerate anion-π catalysis, providing insight into the mechanisms behind inhibition and potential avenues for fine-tuning catalytic reactions. Interestingly, the study did not observe significant autocatalysis, a phenomenon that often characterizes catalytic reactions. Instead, it found evidence of product inhibition, particularly with pyrene interfacers. This discovery suggests that product inhibition is manageable and does not hinder multiple turnovers, particularly in microfluidic reactors.

The core of this research lies in the application of electric field-assisted anion-π catalysis on carbon nanotubes within electrochemical microfluidic reactors. The researchers employed thin fluorinated ethylene propylene (FEP) foils sandwiched between graphite and platinum electrodes, creating an ideal environment for electric field-induced catalysis. Notably, the FEP foils were thin enough to allow current flow without requiring additional electrolytes. By drop-casting MWCNTs onto the graphite electrodes, the researchers effectively created a catalytic surface. They then passed the substrate through the reactor with the aid of a syringe pump. The results were striking; as the current applied to the system increased, so did the conversion of the substrate. Importantly, the relationship between substrate conversion and the mean effective voltage exhibited a quasi-linear dependence, further confirming the occurrence of electric field-induced anion-π catalysis.

In conclusion, the research conducted by Professor Stefan Matile and his team represents a remarkable achievement in the realm of organic synthesis. By effectively combining electrochemical microfluidic reactors with anion-π catalysis on carbon nanotubes, they have ushered in a new era of catalysis where the influence of oriented external electric fields can be harnessed for practical applications. This pioneering work has the potential to revolutionize organic synthesis, offering control over diverse reactions, stereoselectivity, and the emergence of programmable multistep cascades. The future holds great promise for electric field-induced catalysis, as researchers continue to explore the myriad possibilities that this paradigm-shifting approach presents to the field of chemistry.