NUS
Imagination-Inspired Chemical Synthesis through Sustainable Base Metal Catalysis
and Radical Chemistry
Chemical manufacturing is one of the key pillars of the global economy and plays a crucial role in the modern human society. Chemical catalysis is an indispensable tool to promote reactions that enable access to various classes of chemicals, ranging from small-molecule medicines to polymeric materials. Despite considerable advances made in this area, much of it depends on the use of exorbitant and scarce noble metals (such as palladium) to prepare catalysts. Considering the rapidly dwindling abundance of precious metals, this approach cannot continue much longer. More industries have begun an earnest search for sustainable and cost-effective alternatives that are not subject to devastating fluctuations caused by price speculation, a well-known attribute of the precious metal market.
Furthermore, such precious metal-derived catalysts are only capable of mediating a limited range of reactions. As a result, longer synthetic sequences often have to be employed to convert a starting material to the desired target product. Unfortunately, each step in a chemical synthesis process consumes energy, resources and time, and generates waste (spent carbon-based solvents and other by-products) that has to be treated or incinerated. Based on the National Environment Agency (NEA) statistics, about 27,500,000 litres of spent solvents are collected annually in Singapore and subsequently used as supplementary fuel for toxic waste incinerators! Consequently, this leads to more CO2 and other toxic emissions that contribute to global warming, climate change, rising sea levels and other undesirable environmental problems. A lengthy and inefficient chemical synthesis process also means that manpower costs inevitably rise due to a greater demand for workers to carry out the tasks.
Furthermore, chemical synthesis has historically relied on retrosynthetic analysis and target-oriented synthesis, which take advantage of predictable disconnections and established reactions. While highly effective, this logical approach often restricts chemists to familiar chemical space and predictable pathways. By contrast, imagination-inspired synthesis harnesses human creativity and imagination to drive molecular innovation, deliberately seeking out non-intuitive disconnections and unique reaction mechanisms to construct chemical bonds. This approach not only simplifies synthetic routes to complex molecules but also enables access to structurally unprecedented molecular frameworks, enriching our understanding of chemical bonding and molecular behavior. In our group, we leverage the power of human imagination to design new synthetic concepts and transformations that simplify organic synthesis and transform cheap and abundant feedstock chemicals to value-added products with lower environmental footprint.
Ongoing topics of interest include:
(a) Discovery of skeletal editing transformations to access cyclic functional molecules.
(b) Development of peripheral editing transformations for site- and stereoselective functionalization of carbohydrates.
(c) Photochemical, electrochemical and/or base metal-catalyzed synthesis of drug-like molecules.
(d) Discovery of reaction systems that engage radicals in cross-coupling transformations.
(e) Development of catalytic regio- and stereoselective alkene functionalization and deconstruction reactions.
(f) Design of new heterogeneous single-atom catalysts for liquid-phase organic synthesis (collaboration with materials chemists).
(g) Elucidation of reaction mechanisms via mechanistic and computational studies (collaboration with computational chemists).
(h) Plastic waste upcycling using base metal catalysis (collaboration with materials chemists).
Examples of imagination-inspired chemical transformations that we have developed over the years are shown below:
We cordially welcome collaborations in all areas of research including total synthesis, computational chemistry, AI/ML, chemical biology and materials science.
We aspire to be among the top organic chemistry research groups in the world. Students working in the Koh group can expect to be mentored on the process of identifying important problems in chemical synthesis, trained in fundamental research and presentation practices, and groomed to think critically, creatively and independently at the highest level. We work in a close-knit environment where every member has fun and contributes to the success of one another. Members who have worked in our group have went on to establish their own careers and become successful in their own right.
Nature 2024, 631, 319.
Nat. Chem. 2025, 17, 719.
Nature 2025, 647, 906.