A research team from Korea Advanced Institute of Science and Technology (KAIST), led by Professor Sarah Yunmi Lee from the Department of Chemistry, has developed a new method to improve the efficiency of chemical reactions used in creating complex molecules. These molecules are essential for pharmaceuticals and other important chemical applications. The team's approach involves using a special compound called cyclopropenimine (CPI) to control how a copper catalyst behaves during the reaction. This allows the catalyst to generate highly reactive chemical species called radicals and then return to its active state, making the process more efficient. Their findings were published in the Journal of the American Chemical Society. The team used a type of compound known as tertiary alkyl halides, where bromine or chlorine is attached to a carbon atom connected to three other carbon atoms. When the copper catalyst breaks the bond between the carbon and the halogen, a highly reactive radical is formed. This radical then forms a new bond with another part of the same molecule, creating a ring structure. This kind of reaction, known as a radical cyclization, is similar to tying the ends of a string to form a loop. It is a powerful way to build complex molecular structures. In their experiments, the team tested several types of ligands—molecules that bind to the catalyst and influence its activity. They found that simply generating more radicals didn't always result in more of the desired product. Some ligands produced many radicals but failed to create the target compound. However, the best-performing CPI-based ligand allowed for a balanced process, where both radical generation and catalyst regeneration occurred effectively. This led to the successful synthesis of 3,3-disubstituted oxindoles, which are ring-shaped molecules with important applications in medicine and biochemistry. One of the notable achievements of this study is that the team was able to use substrates with bromine atoms at room temperature, which is much milder than the high temperatures often required in similar reactions. They also managed to react compounds with strong carbon-chlorine bonds, which are typically difficult to break. This means that previously challenging compounds, such as tertiary alkyl chlorides, can now be used to make a variety of oxindole compounds that were hard to create before. The key insight from this research is that simply generating radicals is not enough to achieve efficient chemical reactions. Instead, the study shows that balancing the entire catalytic process—both the generation of radicals and the regeneration of the catalyst—is crucial. This balanced approach could lead to the development of more efficient catalysts and expand the range of chemical reactions that can be performed. It may also help researchers build complex molecules needed for pharmaceuticals and other bioactive substances under milder conditions. Professor Sarah Yunmi Lee emphasized that this study highlights the importance of balance within the catalytic cycle. She believes this approach could be applied to new types of radical-based reactions, enabling the use of previously difficult-to-activate substrates in chemical synthesis.