Artful single-atom catalyst for sustainable chemical and pharmaceutical synthesis

National University of Singapore (NUS) chemists have developed an “anchoring-borrowing” strategy, combined with facet engineering, to develop a new class of artful single-atom catalysts (ASACs). These catalysts are formed by anchoring foreign single atoms onto specific facets of reducible support materials, allowing them to bypass the traditional oxidative addition step in cross-coupling reactions, which are widely used in the fine chemical and pharmaceutical industries.

Single-atom catalysts (SACs) are a new type of solid catalyst that have attracted a lot of attention for their ability to maximise the use of every atom and create well-defined, highly active reaction sites. They offer a unique combination of the benefits found in both traditional and modern methods used in making chemicals. In general, the material that holds the metal atom must be designed to keep it stable while allowing it enough flexibility to perform efficiently. However, the strong bonding between the metal atoms and the support, which is needed to prevent the metal atoms from clumping together, can sometimes restrict their reactivity. This limitation can make it challenging for the single metal site to perform well in certain chemical reactions that involve multiple steps, such as cross-coupling reactions.

A research team led by Associate Professor LU Jiong, from the NUS Department of Chemistry developed an “anchoring-borrowing” strategy to create a new class of artful single-atom catalysts. The key idea behind this innovation involves anchoring single metal atoms onto specific sites of metal oxide surfaces. These surfaces can “borrow” oxygen atoms from their surroundings to act as anchor points, while using the metal oxide as an electron reservoir. This unique design allows the structure to adapt and change in a way that avoids the high demand for complex electronic changes in the metal itself, which is a common challenge in traditional cross-coupling reactions. This work is a collaborative effort with Associate Professor WU Jie from the NUS Department of Chemistry, Associate Professor WANG Yang-Gang from Southern University of Science and Technology, China, Assistant Professor WU Dongshuang from Nanyang Technological University, Singapore, and Assistant Professor HAI Xiao from Peking University, China.

This research was published in the journal Nature Communications on 4 April 2025.

The researchers used cerium oxide (CeO₂,110) as the support material and discovered that the resulting Pd₁-CeO₂(110) ASAC works exceptionally well, even with difficult-to-react chemicals such as aryl chlorides and complex compounds. This catalyst outperformed traditional ones, providing high yields, excellent stability, and setting a new benchmark for turnover numbers. This discovery, combined with the ability to produce the catalyst quickly in large amounts, shows the promising potential of ASACs for large-scale production of pharmaceutical ingredients and products.

This research demonstrates that ASACs are highly effective and versatile catalysts for cross-coupling reactions, a key class of transformations in chemical and pharmaceutical manufacturing. Traditional SACs usually struggle with aryl chlorides because the carbon-chlorine bond is very strong and this makes the reaction slow and inefficient. However, ASACs overcome this problem by having a flexible and adaptive active site that enhances the reactivity with aryl chlorides and other demanding substrates, such as heterocyclic compounds, achieving consistently high yields.

ASAC also exhibit broad applicability across other types of reactions, including the Heck reaction (between aryl halides and alkenes), and the Sonogashira reaction (between aryl halides and alkynes), demonstrating its broad potential for a variety of coupling reactions.

Through a combination of experimental and theoretical studies, the researchers found that ASACs work by dynamically changing the structure of the palladium (Pd) atom. The CeO₂ material helps by acting as an electron reservoir, providing electrons to stabilise the Pd atoms and prevent them from becoming over-oxidised. This electron buffering significantly lowers the energy required for the reaction. Advanced X-ray absorption near-edge structure (XANES) measurements confirmed that the Pd atoms maintain their oxidation state nearly unchanged during the reaction, ensuring that the catalyst remains active and stable over time.

Assoc Prof Lu said, “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.”

'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 Assoc Prof Lu.