C-H Activation/Functionalization via Metalla-Electrocatalysis

*Guilherme M. Martins, Najoua Sbei, Geórgia C. Zimmer and Nisar Ahmed*

## **Abstract**

In conventional methods, C−H activations are largely involved in the use of stoichiometric amounts of toxic and expensive metal & chemical oxidants, conceding the overall sustainable nature. Meanwhile, undesired byproducts are generated, that is problematic in the scale up process. However, electrochemical C−H activation via catalyst control strategy using metals as mediators (instead electrochemical substrate control strategy) has been identified as a more efficient strategy toward selective functionalizations. Thus, indirect electrolysis makes the potential range more pleasant, and less side reactions can occur. Herein, we summarize the metallaelectrocatalysis process for activations of inert C−H bonds and functionalization. These Metalla-electrocatalyzed C−H bond functionalizations are presented in term of C−C and C−X (X = O, N, P and halogens) bonds formation. The electrooxidative C−H transformations in the presence of metal catalysts are described by better chemoselectivities with broad tolerance of sensitive functionalities. Moreover, in the future to enhance sustainability and green chemistry concerns, integration of metalla-electrocatalysis with flow and photochemistry will enable safe and efficient scale-up and may even improve reaction times, kinetics and yields.

**Keywords:** metalla-electrocatalysis, C−H bonds activation, catalyst control strategy, mediators, atom and step economy

### **1. Introduction**

The direct functionalization of C–H bonds provides a powerful synthetic pathway for selective C–C and carbon–heteroatom (C–X) bond formation, thus improving atom- and step economy as well as rationalization of chemical synthesis [1, 2]. In the field of conventional C–H activation, prefunctionalization of substrates, generally high temperatures, acidic conditions and/or the use of stoichiometric oxidants (such as a peroxide, a hypervalent iodine) are required due to the high bond dissociation energies, unreactive molecular orbital profiles, low acidities, and ubiquitous nature of the C–H bonds [3, 4]. The stoichiometric amount of reagents/oxidants affect the product's selectivity, additionally the formation of by-products result in overall low turnover of the reaction. Electrochemical C−H functionalization has advantages as this process avoids prefunctionalization of substrates and offering the direct transformation of a simple substrate to a complex and valuable molecule [5]. However, for C–H functionalization, still need a high oxidation potential for selective C–H bonds activation compared

to organic solvents and common functional groups. To overcome this problem, indirect electrolysis via catalysts control strategy (mediators such as redox metal catalysts) is beneficial, makes the potential range more pleasant and has control over selectivity at mild conditions that is not observed through classical catalyst control strategy [6, 7]. From the 90's, great progress was observed in the evolution of reactions involving control of regioselectivity and enantioselectivity. Much of this merit was achieved by the evolution of catalysts based on high-performance transition metals. Derivatives of organic halides, triflates and several other leaving groups are still applied in reactions of aryl alkylations (Friedel-Crafts) and in cross-coupling reactions with several organometallic reagents. In addition, alkenes are also good substrates for aryl alkylation, alkenylation, or for cross-coupling reactions catalyzed by transition metals, using the corresponding halides or correlated substrates. However, most of the known transition metal catalysts do not meet all the requirements of modern developments, and often the biggest limitation is low efficiency and high costs to obtain efficient ligands. Faced with this challenge, there is an increasing use of new technologies applied concurrently to these catalytic systems, making transition metal catalysts more efficient and cleaner, enabling new mechanistic routes [8]. Additionally, the use of electrochemistry concomitant with the chemistry of transition metals offers a powerful strategy, since it avoids the use of external redox additives [9].

Electrocatalysis is a field of electrochemistry that has been gaining great growth in recent years due to the several advantages. In indirect electrosynthetic reactions, the exchange of electrons occurs between a mediator and the organic substrate. Therefore, by varying the applied current or voltage of the power source, the oxidation or reduction capacity of the electrochemical system can be manipulated, this being a great advantage in the method. Likewise, the redox mediator alters the applied potential required for electron transfer, making the potential range more pleasant, and fewer side reactions can occur, avoiding overoxidation, dimerization, parallel reactions or electrode passivation (**Figure 1**). In addition, electrocatalysis deals with the development for energy storage, solar fuels, fuel cells, and also other electrochemical devices with charge transfer reactions interfacial control [10].

Whereas the redox potentials and the selectivity of the reaction can be controlled by changing the ligand of the mediators of the complex transition metals. With the use of electrochemistry this process can become more selective, due to the possibility of controlling the electrical potential of the reaction

**Figure 1.**

*General illustration of indirect anodic transformation.*

*C-H Activation/Functionalization via Metalla-Electrocatalysis DOI: http://dx.doi.org/10.5772/intechopen.95517*

#### **Figure 2.**

*General mechanism for cross-coupling reactions with transition metal mediator.*

**Figure 3.** *Cell notations.*

medium by changing the voltage (V) or the electric current (A) through the energy source (**Figure 2**) [11].

Considering this, we have prepared an overview of the recent metallaelectrocatalysis process for activation/functionalization of inert C−H bonds. The perspective and limitations together with mechanistic discussions will be presented.

To offer an easy interpretation of the different catalytic systems discussed here, we will use a standardized notation, differentiating the divided cell from the undivided cell, as well as if the reaction follows via constant current or constant potential (**Figure 3**). Additionally, the different types of electrodes will be added along with other details, offering a better experience for the reader.
