Decarboxylative Transformations in Organic Synthesis

Decarboxylative transformations have emerged as a compelling strategy for the construction of carbon–carbon and carbon–heteroatom bonds by exploiting the ubiquity of carboxylic acids as traceless precursors. Removal of the carboxylate moiety generates carbon-centred radicals or organometallic intermediates that can engage in diverse bond-forming processes under mild conditions. Recent advances have harnessed photoredox and electrocatalytic methods, as well as earth-abundant metal catalysts, to achieve selective decarboxylation of aliphatic, aromatic and heteroaromatic acids. These protocols offer high atom economy and functional-group tolerance, and permit late-stage modification of complex molecules, including drug candidates and biomass-derived feedstocks. Mechanistic studies reveal that controlled radical generation, single-electron transfers and ligand-to-metal charge‐transfer events underpin the breadth of decarboxylative coupling, halogenation, oxygenation and other functionalisation reactions now available to synthetic chemists.

Research from Nature Portfolio

Recent studies have demonstrated a Brønsted acid-activated iron photocatalytic system that exploits ligand-to-metal charge transfer for the decarboxylative activation of haloalkyl carboxylates. Under visible-light irradiation, an in situ assembly of FeIII centres, carboxylate anions and proton donors facilitates efficient electron transfer to generate alkyl radicals. These radicals undergo fluoro-polyhaloalkylation of unactivated alkenes, providing access to valuable alkyl fluoride motifs under mild, sustainable conditions. Mechanistic investigations suggest that acid-mediated hydrogen bonding enhances charge‐transfer efficiency, offering a blueprint for further use of earth-abundant metals in decarboxylative radical chemistry.

Decarboxylative Transformations in Organic Synthesis publication trend

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

Technical terms

Decarboxylation: Removal of a carboxyl group from a molecule, releasing carbon dioxide and generating a reactive intermediate.

Photoredox catalysis: Use of light to drive redox reactions via a photocatalyst that alternates between oxidised and reduced states.

Ligand-to-metal charge transfer (LMCT): Photoinduced electron transfer from a ligand to the metal centre within a coordination complex.

Carboxylate: The anionic form of a carboxylic acid (R–COO−) that often serves as a precursor to radical or organometallic species.

Radical intermediate: A highly reactive species containing an unpaired electron, capable of undergoing rapid bond-forming reactions.

References

1. Iron photocatalysis via Brønsted acid-unlocked ligand-to-metal charge transfer. Nature Communications (2024).
2. Photoredox‐Catalyzed Decarboxylative Bromination, Chlorination and Thiocyanation Using Inorganic Salts. Angewandte Chemie International Edition (2023).
3. Decarboxylative sulfoximination of benzoic acids enabled by photoinduced ligand-to-copper charge transfer. Chemical Science (2022).
4. Decarboxylative oxygenation of carboxylic acids with O 2 via a non-heme manganese catalyst. Green Chemistry (2022).