Electro-Organic Synthesis: Next Emerging Technique

Industrial developments, excessive energy consumption, sustainable technologies, environmental cleaning processes are major topics of political and social discourse. Current innovations are rated not only focusing on their benefit and utility but also concerning their eco-friendly approaches. The development of green technological processes is becoming more important and requires harmless energy sources. Particularly over the past decade, the severe limitations of fossil resources intensify the movement towards sustainable synthesis techniques with a strict cutback in the ecological footprint [1].

Electro-organic synthesis belongs to the synthetic organic chemistry discipline that facilities the direct use of electricity to generate valuable compounds. Hence, it is possible to transfer green aspects of sustainable energy sources to the whole production process [2]. Since the Kolbe’s discoveries of using electricity as a reagent for organic transformations over 170 years ago, this technique has not been accepted by the broad organic chemistry community, although less hazardous materials are being used. Recently, several groups have shown interest and exploring this subject to provide sufficient knowledge for further research.

D. Pollok and S. R. Waldvogel from Johannes Gutenberg University Mainz, Germany reported a review article about “Electro-organic synthesis – a 21^st century technique” in Chemical Science (2020) [3]. In this E-content, we are highlighting the topics with essential pathway towards future views to our blog readers.

Electro-organic synthesis is involved in following research areas such as electrocatalysis, redox-tags, the cation-pool method, bio-electrochemistry, and electro-organic synthesis in a continuous flow. These techniques have also gained significant attention from industry and open pathways for various novel developments.  However, we can identify many research articles turns towards and encouraging the use of this method by showing the process simplicity. The fundamental principles of this synthetic process involved in redox reactions. 

Baran and co-workers published a general overview of electro-organic developments since 2000 [4]. In this article they completely reviewed on synthetic developments with great importance in contemporary synthesis: 

• Electrochemical fluorination.
• Electrochemical C-N functionalization of arenes.
• Kolbe electrolysis.
• Electrochemical arene couplings.
• Electrochemical construction of heterocycles.
• Electrochemistry in the synthesis of natural products related compounds, and late-stage functionalization.

Figure 1. The schematic diagram of some of the organic compounds is synthesized by electro-organic method [2].

Electro-organic method to solve the challenges in synthetic organic chemistry:

First, carbon–carbon bond formation has been a crucial tool in synthetic organic chemistry over years of research and is an integral part of organic synthesis. Organo-catalysis or transition metal-based catalysts are used to selectively form these bonds. Scientists have been reported on the formation of C-C bond in the organic synthetic process. In particularly, Little et al. investigated electro-organic approaches such as reductive carbon–carbon couplings with olefin and carbonyl compounds focused on mechanistic themes to provide deeper insight into electro-organic reaction mechanisms [5]. Schafer et al. used Kolbe electrolysis for cascade reactions, forming novel carbon–carbon bonds in complex architectures [6].

Secondly, the major role challenges in organic chemistry are direct, selective C–H activation due to the high oxidation potentials. In this regard, Moeller et al. have established anodic olefin coupling reactions to access cyclic substrates which include sophisticated functionalities using a conventional 6 V battery in an undivided beaker cell [7]. Yoshida et al. have the major contributions in direct electrochemical C–H activation with the development of the “cation-pool” method.

Thirdly, the challenge on the formation of biaryls, which are highly important for materials science and active pharmaceutical ingredients (APIs), which occurs in natural products, electro-organic transformations with a broad variety of possibilities. Waldvogel et al. have synthesized several symmetric and non-symmetric biphenyls as well as phenol–(hetero)arene cross-coupled products with reagent- and metal-free electro-organic protocols [8].

In comparison to photo-redox catalysis, electro-catalysis process can not only use a small part of the solar spectrum but can take advantage of the whole energy range without loss [9].

Ackermann and his research team are the leaders in this field. They found an outstanding property for cobalt electro-catalysts in oxidations involving alcohols, alkenes, alkynes, amines, allenes, carbon monoxide, carboxylic acids, and isocyanides [9]. 

Some of the important parameters that are considered for developing this field in the near feature:

• A major criterion is the parameter of reproducibility of experiments which is accompanied by a variety of different parameters influencing the reaction.
• The development of novel electrode materials enhances the performance of electro-organic conversions.
• A major drawback of electro-organic transformations is the long reaction time due to the sensitivity of substrates towards higher current densities, which hampers broader acceptance of the technique in organic chemistry laboratories.
• The development of novel processes is driven by the issues of sustainability and cost-efficiency.
• Despite the successful development of electro-organic processes, the challenging task of scale-up for industrial applications has to be faced.
• The major advantage of electro-organic synthesis in comparison to conventional transformation is the absence of metal contamination in the products if carbon allotropes are used as electrodes, which is highly favored in the synthesis of APIs.
• Electro-organic synthesis possesses several relevant features for these syntheses like mild reaction conditions, shortened pathways, atom- and cost efficiency, and avoidance of (over-)stoichiometric hazardous reagents. However, electro-organic conversions of complex molecules are still rare because most electro-organic protocols use ordinary substrates containing a single redox-active functionality.
• The synthesis of natural products requires the installation of chiral information. In comparison to conventional asymmetric catalysis, only a few electro-organic conversions facilitate asymmetric reactions, commonly with unsatisfactory enantiomeric excess.
• Electrochemistry has exhibited powerful capabilities and can be combined with renewable feedstocks for the generation of fuels and chemicals.
• Electro-chemical water splitting is a current topic of research for producing high-quality hydrogen and oxygen. However, the over-potential for oxygen evolution within water splitting is still a major issue.
• Electro-organic conversions have emerged at a rapid speed, providing numerous techniques. Reports usually provide a mechanistic rationale for the electro-organic transformation observed.

Future Perspectives

Over the last few decades, more significant progress was made in this field. Many research groups are now focusing on this topic as it combines various advantages of social and political importance with efficient synthetic applications. 

Our SNB Team recommended this research article to help the reader to know about the electro-organic synthesis, a future emerging technique which belongs to the synthetic organic chemistry discipline for the usage of electricity to generate valuable compounds. The successful conversions of renewable bio-based feedstocks are the first evidence of its potential in research. Renewable electricity sources and the electrosynthesis of value-added chemicals together will be a game-changer for the chemical industries in the near future.

 References

1. R. Cernansky, Nature, 519, 379 (2015).
2. A. Wiebe, et al., Angew. Chem. Int. Ed. 57, 5594 (2018).
3. D. Pollok and S. R. Waldvoge, Chem. Sci., (2020) DOI: 10.1039/d0sc01848a.
4. P. S. Baran, et al., Chem. Rev. 117, 13230 (2017).
5. R. D. Little and M. K. Schwaebe, in Electrochemistry VI Electroorganic Synthesis: Bond Formation at Anode and Cathode, Springer Berlin Heidelberg, Berlin, Heidelberg, 185,1–48 (1997).
6. Schafer, et al. Angew. Chem., Int. Ed. Engl., 23, 980 (1984).
7. K. D. Moeller, et al., Green Chem., 16, 69 (2014).
8. S. R. Waldvogel, et al., Acc. Chem. Res., 53, 45 (2020).
9. L. Ackermann, Acc. Chem. Res., 53, 84 (2020).

Blog Written By

Dr. A. S. Ganeshraja

Assistant Professor

National College, Tiruchirappalli

Tamil Nadu, India

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Dr. K. Rajkumar

Dr. S. Chandrasekar

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Dr. Y. Sasikumar

Dr. K. Vaithinathan

Dr. S. Thirumurugan