According to a study published in Nature Communications, a research team led by Associate Professor Jiong Lu from the Department of Chemistry at the National University of Singapore devised an “anchoring-borrowing” technique to construct a new class of artistic single-atom catalysts (ASAC).
a) Rational design of ASAC for cross-coupling reactions, where M1 represents the foreign single metal atom introduced onto the reducible carriers. (b) Using a single atom of Pd1 anchored on the material CeO2 as a representative example, this panel illustrates the dynamic structural and valence state evolution of the Pd1 ASAC. These changes help it avoid the usual challenge in cross-coupling reactions, which is the energy barrier associated with oxidative addition. This contrasts with traditional homogeneous catalyst systems, where the reaction rate is largely limited by this step. Image Credit: Nature Communications.
These catalysts are created by attaching foreign single atoms to certain aspects of reducible support materials. This allows them to skip the typical oxidative addition phase in cross-coupling processes, which are widely employed in the fine chemical and pharmaceutical industries.
Single-atom catalysts (SACs) are a new form of solid catalyst that has received much attention due to their capacity to make the best use of each atom and create well-defined, highly active reaction sites. They provide a unique blend of benefits seen in both traditional and modern chemical production methods.
Generally, the material that supports the metal atom must be engineered to keep it stable while allowing sufficient flexibility to work efficiently. However, the strong bonding between the metal atoms and the support required to keep the metal atoms from clumping together can occasionally limit their reactivity. This constraint can make it difficult for a single metal site to perform well in chemical reactions with several stages, such as cross-coupling.
The main idea behind this discovery is to bind single metal atoms to specified places on metal oxide surfaces. These surfaces can “borrow” oxygen atoms from their surroundings to serve as anchor points, while the metal oxide functions as an electron reservoir. This novel design enables the structure to adapt and evolve while avoiding the significant requirement for intricate electronic changes in the metal itself, which is a major issue in standard cross-coupling reactions.
This study was conducted in collaboration with Associate Professor Jie Wu of NUS Chemistry, Associate Professor Yang-Gang Wang of Southern University of Science and Technology in China, Assistant Professor Dongshuang Wu of Nanyang Technological University in Singapore, and Assistant Professor Xiao Hai of Peking University in China.
The researchers employed cerium oxide (CeO2,110) as the support material and discovered that the resulting Pd1-CeO2(110) ASAC performs very well, even with difficult-to-react chemicals like aryl chlorides and complicated compounds. This catalyst beat standard ones by producing high yields, maintaining outstanding stability, and setting a new turnover benchmark.
This discovery and the capacity to generate the catalyst quickly and in huge quantities demonstrate ASACs’ tremendous potential for large-scale pharmaceutical ingredient and product manufacturing.
This study shows that ASACs are very effective and adaptable catalysts for cross-coupling reactions, a common type of transformation in chemical and pharmaceutical manufacturing. Traditional SACs usually struggle with aryl chlorides because the carbon-chlorine bond is extremely strong, making the reaction sluggish and inefficient.
However, ASACs circumvent this issue by having a flexible and adaptive active site that improves reactivity with aryl chlorides and other challenging substrates, such as heterocyclic compounds, resulting in consistently high yields.
ASAC also has broad applicability in other types of reactions, such as the Heck reaction (between aryl halides and alkenes) and the Sonogashira reaction (between aryl halides and alkynes), indicating its versatility in coupling reactions.
Through a combination of experimental and theoretical studies, the researchers discovered that ASACs function by dynamically modifying the structure of the palladium (Pd) atom. The CeO2 material contributes by functioning as an electron reservoir, providing electrons to stabilize the Pd atoms and keep them from over-oxidizing.
This electron buffering considerably reduces the energy needed for the process. Advanced X-ray absorption near-edge structure (XANES) studies demonstrated that the Pd atoms' oxidation status remained essentially constant, confirming that the catalyst remained active and stable throughout time.
The new concept of heterogeneous ASACs provides a much greener way to tackle the long-standing challenge of oxidative addition in cross-coupling reactions. This strategy goes beyond the limitations of traditional homogeneous and heterogeneous catalysts, and holds great potential for large-scale, sustainable production of fine chemicals and pharmaceuticals.
Jiong Lu, Associate Professor, Department of Chemistry, National University of Singapore
“Looking ahead, we plan to extend this approach to a wider range of metals that can be used in cross-coupling reactions. By adjusting the types and combinations of single atoms and support materials, we could enhance the performance of more abundant, non-precious metals in these reactions,” added Prof Lu.
Journal Reference:
Shi, J., et al. (2025) Defying the oxidative-addition prerequisite in cross-coupling through artful single-atom catalysts. Nature Communications. doi.org/10.1038/s41467-025-58579-8