Electrochemical Methods in Organic Synthesis

The electrochemical approach to organic synthesis uses electrical current as a clean reagent to drive oxidation and reduction events at electrode surfaces, generating reactive intermediates—radical cations, radical anions and neutral radicals—under mild conditions. These species can effect bond formations ranging from C–C coupling and C–H functionalisation to heterocycle assembly without the need for stoichiometric chemical oxidants or reductants. Metal‐catalysed and metal‐free protocols coexist, the latter often employing organic redox mediators or electroauxiliaries to fine-tune reactivity. Advances in cell design, including undivided cells, divided cells and flow reactors, have improved scalability and electrode longevity. Late‐stage functionalisation of complex molecules demonstrates the potential for rapid diversification of pharmaceuticals and natural products. Collectively, these developments point toward sustainable manufacturing of fine chemicals, agrochemicals and functional materials while reducing waste and energy consumption.

Research from Nature Portfolio

Metal-free electrochemical dihydroxylation of unactivated alkenes demonstrates the power of anodic oxidation to install vicinal diols under ambient conditions without transition-metal catalysts or chemical oxidants. The protocol tolerates a broad range of alkenes, including natural product derivatives, and proceeds via identifiable iodohydrin and epoxide intermediates. Scalable 1,2-diamination of alkenes employs an organic redox catalyst to deliver diamines with excellent diastereoselectivity, obviating transition-metal species and ensuring broad functional-group compatibility. Electrooxidative para-selective C–H/N–H cross-coupling utilises undivided cells to assemble triarylamine frameworks with exclusive para-regioselectivity and concurrent hydrogen evolution, showcasing an external-oxidant-free, atom-economic route to C–N bond formation.

Electrochemical Methods in Organic Synthesis publication trend

The graph below shows the total number of articles in electrochemical methods in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Electrosynthesis: Organic synthesis driven by electrical current to generate reactive species at electrodes.

Anodic oxidation: Oxidation process occurring at the anode, yielding cationic or radical intermediates.

Electrocatalysis: Use of catalysts in an electrochemical cell to lower reaction potentials and improve selectivity.

Redox mediator: Species that shuttles electrons between the electrode and substrate to facilitate electron transfer.

Radical intermediate: Highly reactive species bearing an unpaired electron formed during electron-transfer steps.

Hydrogen atom transfer (HAT): Mechanism in which a hydrogen atom is moved between a radical and a substrate, often mediated by electrogenerated species.

References

1. Electrochemical Late-Stage Functionalization. Chemical Reviews (2023).
2. Metal-free electrochemical dihydroxylation of unactivated alkenes. Nature Communications (2023).
3. Electrochemically Driven Hydrogen Atom Transfer Catalysis: A Tool for C(sp3)/Si–H Functionalization and Hydrofunctionalization of Alkenes. ACS Catalysis (2023).
4. Electrochemical strategies for C–H functionalization and C–N bond formation. Chemical Society Reviews (2018).
5. Electrooxidative para-selective C–H/N–H cross-coupling with hydrogen evolution to synthesize triarylamine derivatives. Nature Communications (2019).
6. Practical and stereoselective electrocatalytic 1,2-diamination of alkenes. Nature Communications (2019).