Transition Metal-Catalyzed Hydroacylation Reactions

Transition metal-catalysed hydroacylation represents a powerful strategy for the direct formation of ketones by addition of the formyl C–H bond of an aldehyde across unsaturated substrates such as alkenes, alkynes or strained rings. The general catalytic cycle begins with oxidative addition of the aldehyde C–H bond to a low-valent metal centre, followed by migratory insertion of the π-bond into the resulting metal–hydride or metal–acyl intermediate and concluding with reductive elimination to release the ketone product and regenerate the active catalyst. Rhodium complexes have historically dominated this field, but recent ligand and catalyst design has broadened the palette to include cobalt, nickel, ruthenium and iridium systems. Key challenges include suppression of competing aldehyde decarbonylation and control of regio- and enantioselectivity. Chelating and directing groups on the aldehyde or unsaturated partner often stabilise crucial intermediates and enable fine-tuning of reactivity. The resulting ketones serve as versatile building blocks in the synthesis of natural products, heterocycles and pharmaceutical scaffolds, illustrating the global significance of hydroacylation in sustainable and step-economic synthesis.

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Transition Metal-Catalyzed Hydroacylation Reactions publication trend

The graph below shows the total number of articles in transition metal-catalyzed hydroacylation reactions across all publications each year (not limited to Nature Index journals).

Technical terms

Oxidative addition: Insertion of a metal centre into a σ-bond (e.g. C–H) with an increase in metal oxidation state.

Migratory insertion: Insertion of an unsaturated substrate (alkene or alkyne) into a metal–hydride or metal–acyl bond.

Reductive elimination: Coupling of two ligands on a metal to form a new σ-bond and regenerate the lower-valent catalyst.

Chelation: Coordination of a substrate through two donor atoms to stabilise a metal-bound intermediate and influence selectivity.

References

1. Recent advances in transition metal-catalysed hydroacylation of alkenes and alkynes. Organic Chemistry Frontiers (2016).
2. Exploiting Carbonyl Groups to Control Intermolecular Rhodium-Catalyzed Alkene and Alkyne Hydroacylation. Journal of the American Chemical Society (2017).
3. Catalytic asymmetric hydrometallation of cyclobutenes with salicylaldehydes. Chemical Science (2021).