Palladium-Catalyzed Acylation Reactions in Organic Synthesis

Palladium-catalysed acylation has emerged as a cornerstone in modern synthetic chemistry, enabling efficient construction of ketones and related carbonyl frameworks under mild conditions. Central to these transformations are the elementary steps of oxidative addition, in which an acyl electrophile inserts into a Pd(0) centre; transmetalation or migratory insertion, whereby an organic fragment transfers to palladium; and reductive elimination, which liberates the ketone product and regenerates the active catalyst. Beyond classical cross-coupling of acid chlorides and organometallic reagents, recent advances exploit decarboxylative pathways, direct C–H activation and photoredox co-catalysis to access acyl partners from simple carboxylic acids, aldehydes or pre-functionalised substrates. The use of removable or innate directing groups has unlocked site-selective acylation of (hetero)arenes, while chiral ligands and transient mediators are beginning to address longstanding challenges in enantioselective ketone synthesis. These methodologies have found application in the rapid assembly of pharmaceutical intermediates, agrochemicals and functional materials, offering improved atom economy and reduced waste compared with conventional Friedel–Crafts or stoichiometric metal-mediated processes. Ongoing efforts focus on expanding substrate scope, enhancing regio- and stereocontrol, and integrating sustainable oxidants or light-driven activation to meet the demands of green and scalable production.

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Palladium-Catalyzed Acylation Reactions in Organic Synthesis publication trend

The graph below shows the total number of articles in palladium-catalyzed acylation reactions in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Oxidative addition: Insertion of Pd(0) into an acyl–halide bond to form a Pd(II) complex.

Transmetalation: Transfer of an organic fragment from one metal species to the palladium centre.

Reductive elimination: Coupling of two ligands on Pd(II) to release the ketone and regenerate Pd(0).

Directing group: A functional moiety that coordinates to palladium to control site-selective C–H activation.

Decarboxylative acylation: Generation of an acyl-Pd species by loss of CO₂ from a carboxylic acid or derivative.

C–H activation: Direct cleavage of a carbon–hydrogen bond by palladium to enable functionalisation at unactivated positions.

References

1. Pd-Catalyzed Aromatic Dual C-H Acylations and Intramolecular Cyclization: Access to Quinoline-Substituted Hydroxyl Isoindolones. Molecules (2024).
2. A Palladium-Catalyzed 4CzIPN-Mediated Decarboxylative Acylation Reaction of O-Methyl Ketoximes with α-Keto Acids under Visible Light. Molecules (2022).
3. Pd(II)-Catalyzed C-H Acylation of (Hetero)arenes—Recent Advances. Molecules (2020).