# New Palladium-Catalyzed Chemical Reaction Discovered Scientists develop efficient method for ketone homologation. - **Source:** [Nature](https://brifing.si/source/4d850c3b-dd79-4024-bc91-db2571889199) - **Published:** 2026-09-03 - **Topic:** [Data & AI](https://brifing.si/c/data-ai) - **Original article:** - **On Brifing:** https://brifing.si/s/af2f434d-a5ea-4e0b-a31a-4c070a05e714 ## Novel Reaction Mechanism Researchers at EPFL developed a new palladium-catalyzed method for decarboxylative rearrangement of β-hydroxy carboxylic acids. Known since the 1960s, this reaction was inefficient due to radical and carbocationic byproducts. The new method proceeds via six-membered Pd(IV) chelate formation, enabling precise stereochemical control. ## Chemical Process Details The reaction involves carbon migration from β to α position with CO2 extrusion. Palladium(IV) serves as redox center. The closed-shell mechanism preserves absolute configuration of migrating carbon while inverting α-stereocenter. This offers significant advantages over classical Tiffeneau-Demjanov reactions. ## Application Scope The method works effectively on both cyclic and acyclic ketones/aldehydes. Avoiding hazardous diazo reagents provides industrial advantages. It served as key step in (+)-rupestine D total synthesis, opening new possibilities in carbon skeleton editing. ## Stereochemical Control The reaction's major advantage lies in enhanced migration selectivity and stereochemical fidelity. For unsymmetrical ketones, migrating group selectivity significantly surpasses classical methods. This feature proves crucial for complex molecule synthesis. ## Historical Development Decarboxylative semi-pinacol rearrangement was first reported in 1960. However, side reactions and poor stereocontrol limited its utility for six decades. The new Pd-catalyzed approach overcomes these historical challenges, marking a paradigm shift. ## Industrial Potential The process holds broad application potential in pharmaceutical and fine chemical industries. It could save time and costs in natural product synthesis and drug development. Avoiding hazardous chemicals also benefits scale-up efforts. ## Scientific Impact Published in Nature, this work establishes new paradigm in chemical synthesis. Expanding palladium catalysts' use in C-C bond formation, this discovery will likely trigger new research directions in organic chemistry. ## Future Directions Researchers plan to test the method's compatibility with other functional groups. Developing enantioselective versions could revolutionize asymmetric synthesis. This breakthrough heralds significant advances in sustainable chemistry. ## Sources covering this story - https://www.nature.com/articles/s41586-026-11091-5 — --- _Summary written by Brifing from the original reporting. Copyright in the original article belongs to its publisher; read the full piece at the link above._