Synthesis Strategies for Dicarbonyl Compounds

Dicarbonyl compounds, characterised by the presence of two carbonyl functionalities within a single molecule, occupy a central place in organic synthesis due to their versatility as building blocks for pharmaceuticals, agrochemicals and advanced materials. Classical approaches rely on carbon–carbon bond-forming condensations such as the Claisen and Dieckmann reactions to assemble 1,3-diketones, while Reformatsky and Stetter protocols enable access to β- and γ-diketone motifs under varied conditions. More recent developments have harnessed ketene intermediates generated in situ from precursors such as acyl triazoles or benzothiazolones to deliver acyclic and heterocyclic dicarbonyl scaffolds via cycloadditions. Acid-promoted cyclizations and decarboxylative couplings offer streamlined routes to cyclic frameworks, including pyrones and cyclopentenones, emphasising atom economy and step reduction. Organocatalytic and metal-catalysed variants further expand the methodological landscape, allowing for enantioselective and regioselective access to complex dicarbonyl architectures. Across these strategies, a growing emphasis on green chemistry has driven the adoption of solvent-free protocols, water-mediated processes and recyclable catalysts, underscoring the global imperative for sustainable synthesis.

Research from Nature Portfolio

No recent Nature Portfolio content available.

Synthesis Strategies for Dicarbonyl Compounds publication trend

The graph below shows the total number of articles in synthesis strategies for dicarbonyl compounds across all publications each year (not limited to Nature Index journals).

Technical terms

Dicarbonyl compound: An organic molecule bearing two carbonyl (C=O) groups, which may be adjacent (1,2-diketone) or separated by one or more atoms (e.g. 1,3-diketone).

1,3-Diketone (β-diketone): A dicarbonyl in which two carbonyls are separated by a single methine or methylene unit, enabling keto–enol tautomerism and versatile reactivity.

Ketenes: Highly reactive cumulated species with the general formula R2C=C=O, often generated in situ for cycloadditions and acylation reactions.

Decarboxylative coupling: A strategy in which a carboxylate unit is expelled as carbon dioxide to facilitate formation of a new carbon–carbon bond, often under metal or organocatalytic conditions.

Atom economy: A metric of synthetic efficiency defined as the proportion of the reactant atoms incorporated into the desired product, promoting sustainability by minimising waste.

References

1. Approach to Pyrido[2,1-b][1,3]benzothiazol-1-ones via In Situ Generation of Acyl(1,3-benzothiazol-2-yl)ketenes by Thermolysis of Pyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones. Molecules (2023).
2. Recent Developments in the Synthesis of β-Diketones. Pharmaceuticals (2021).
3. Atom-Economic Synthesis of 4-Pyrones from Diynones and Water. Molecules (2017).
4. Synthesis of γ-pyrones via decarboxylative condensation of β-ketoacids. Monatshefte für Chemie - Chemical Monthly (2016).
5. 2-(2-(Dimethylamino)vinyl)-4H-pyran-4-ones as Novel and Convenient Building-Blocks for the Synthesis of Conjugated 4-Pyrone Derivatives. Molecules (2022).