Catalytic Oxidation of Olefins to Ketones

The catalytic oxidation of olefins to ketones represents a cornerstone transformation in synthetic chemistry, enabling the direct conversion of readily available alkenes into valuable carbonyl compounds. Central to this process is the activation of the carbon–carbon double bond by a transition‐metal catalyst, often in concert with a co-oxidant, to deliver ketones with high regio- and chemoselectivity. Historically dominated by the palladium-catalysed Wacker oxidation, recent advances have diversified the catalyst portfolio to include earth-abundant metals, redox-active ligands and benign oxidants. These developments have expanded substrate scope to include internal and non-activated olefins, improved environmental credentials by replacing stoichiometric reagents with air or hydrogen peroxide, and delivered enantioselective variants. Mechanistic insights—ranging from chain-walking pathways to ligand noninnocence—have underpinned rational catalyst design, while applications span fine-chemical synthesis, pharmaceutical manufacture and large-scale commodity processes.

Research from Nature Portfolio

Recent studies have demonstrated a nickel-catalysed remote Wacker-type oxidation capable of targeting unactivated internal olefins through a chain-walking mechanism. Using ambient air as the sole oxidant and polymethylhydrosiloxane as a hydride source at room temperature, this method achieves excellent regio- and chemo-selectivity, converting challenging substrates into ketones without reliance on directing groups. The naturally abundant nickel catalyst and mild conditions enable direct functionalisation of complex molecular frameworks, providing access to medicinally relevant motifs from simple olefinic precursors.

Catalytic Oxidation of Olefins to Ketones publication trend

The graph below shows the total number of articles in catalytic oxidation of olefins to ketones across all publications each year (not limited to Nature Index journals).

Technical terms

Olefins: Unsaturated hydrocarbons containing at least one carbon–carbon double bond.

Ketones: Organic compounds featuring a carbonyl group bonded to two carbon atoms.

Wacker oxidation: A catalytic reaction converting olefins to ketones via metal-mediated activation of the double bond and subsequent oxygen insertion.

Chain-walking: A mechanism in which a catalyst migrates along a carbon chain through successive β-hydride elimination and reinsertion steps.

Redox noninnocence: The ability of a ligand to participate in electron transfer, altering the apparent oxidation state of the metal–ligand ensemble.

Markovnikov selectivity: The preference for addition of a reagent to the more substituted carbon of an unsaturated substrate, leading to the more stable carbocation intermediate.

Catalyst turnover: The total number of substrate molecules transformed by a single catalyst molecule before deactivation.

References

1. Nickel-catalyzed remote and proximal Wacker-type oxidation. Communications Chemistry (2019).
2. Wacker Oxidation of Methylenecyclobutanes: Scope and Selectivity in an Unusual Setting. Angewandte Chemie International Edition (2023).
3. Chemical and Redox Noninnocence of Pentane-2,4-dione Bis(S‑methylisothiosemicarbazone) in Cobalt Complexes and Their Application in Wacker-Type Oxidation. JACS Au (2024).
4. Sustainable Wacker‐Type Oxidations. Angewandte Chemie International Edition (2022).