Catalytic Carboxylation Processes in Organic Synthesis

Catalytic carboxylation harnesses carbon dioxide as a sustainable C1 feedstock to construct C–C bonds and generate carboxylic acids under mild conditions. Advances in metal-catalysed, photoredox-mediated and electrochemical strategies have enabled the direct incorporation of CO₂ into alkenes, (pseudo)halides, aromatic C–H bonds and imines. These methods overcome the intrinsic thermodynamic stability and kinetic inertness of CO₂ by employing tailored catalysts or light-driven electron-transfer pathways to activate substrates at ambient pressure and temperature. Broad substrate scopes, high chemo- and regioselectivities, low catalyst loadings and facile downstream derivatisation have been demonstrated. Applications span the synthesis of bioactive molecules, functional materials and intermediates for fine-chemical production, underscoring the potential of catalytic carboxylation for carbon capture and utilisation within a circular carbon economy.

Research from Nature Portfolio

Recent studies have introduced a visible-light photoredox system that effects arylcarboxylation of unactivated alkenes with atmospheric CO₂. This approach proceeds at room temperature under 1 atm CO₂, delivering a diverse array of bicyclic and heterocyclic acetic acids with high regio- and chemoselectivity. Mechanistic investigations support in situ generation of a CO₂•– radical anion followed by radical addition and subsequent CO₂ incorporation, offering a mild and scalable route to functionalised carboxylic acids. In parallel, an electro-reductive nickel-catalysed protocol has been developed for the carboxylation of unactivated aryl chlorides and alkyl bromides. Using electrons as the sole reductant, this method operates under mild conditions with inexpensive ligands, safe and reusable electrodes, and displays broad functional-group tolerance. Detailed electrochemical studies reveal a Ni(0)/Ni(I)/Ni(II) catalytic cycle and highlight the role of oxidative addition and reductive CO₂ insertion in achieving efficient C–CO₂ bond formation.

Catalytic Carboxylation Processes in Organic Synthesis publication trend

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

Technical terms

Carboxylation: Introduction of a carboxyl group (–CO₂H) into an organic molecule using CO₂.

Photoredox catalysis: Light-driven redox activation of catalysts to generate reactive radical or ionic intermediates.

Electrocatalysis/Electroreduction: Use of electrical potential and catalysts to promote reduction or oxidation reactions at electrodes.

C–H activation: Direct functionalisation of carbon–hydrogen bonds without prior substrate derivatisation.

Regioselectivity: Preference for bond formation at one spatial position over others on a molecule.

Umpolung: Strategy to invert a functional group's normal polarity to enable unconventional bond disconnections.

References

1. Arylcarboxylation of unactivated alkenes with CO2 via visible-light photoredox catalysis. Nature Communications (2023).
2. Nickel-catalyzed electrochemical carboxylation of unactivated aryl and alkyl halides with CO2. Nature Communications (2021).
3. Electroreductive Cobalt‐Catalyzed Carboxylation: Cross‐Electrophile Electrocoupling with Atmospheric CO2. Angewandte Chemie International Edition (2020).
4. Direct electrochemical defluorinative carboxylation of α-CF 3 alkenes with carbon dioxide. Chemical Science (2020).
5. Recent advances in electrochemical carboxylation reactions using carbon dioxide. Green Chemical Engineering (2022).