A research team led by Do Hyun Ryu in the Department of Chemistry at Sungkyunkwan University (SKKU) has developed two new methods for creating complex molecules with high precision using chiral organic catalysts. These catalysts are molecules that can influence the three-dimensional shape of the products formed in chemical reactions. The studies, both published in Angewandte Chemie International Edition, show how a single catalyst can be used to control multiple types of reactions, making the synthesis of complex structures more efficient and selective. In the first study, Ryu's team collaborated with Hyunwoo Kim’s group at the Korea Advanced Institute of Science and Technology (KAIST) to create a versatile catalytic system. This system uses a single chiral catalyst to perform two different types of carbon-carbon bond-forming reactions with high selectivity. One of these reactions, an asymmetric allylation, had previously been difficult to control. The same catalyst was also used for an aldol reaction, a common reaction in organic chemistry. The key breakthrough is that the catalyst can selectively activate the desired reaction site and control the three-dimensional structure of the resulting molecules. This allows for the synthesis of a wide range of chiral compounds with high precision. The products from these reactions were used to create biologically active natural products, such as (+)-dimethyl citramalate. Computational models, specifically density functional theory (DFT) calculations, helped explain how the catalyst controls both the reaction site and the final structure of the molecules. In the second study, the team developed a new method for creating tetrahydrofuran ring structures, which are five-membered rings containing one oxygen atom. These rings are commonly found in many natural products and pharmaceuticals. Traditionally, synthesizing such complex structures required starting materials that already had specific stereochemistry. However, the new method uses a chiral catalyst to construct multiple stereocenters (points where atoms are arranged in three-dimensional space) from simple starting materials that lack pre-existing stereochemistry. This approach allows for greater flexibility in molecule design. The resulting compounds can be further transformed into more complex structures, and the method was successfully used to create a synthetic intermediate for (+)-altholactone, a natural product with potential anticancer properties. Although the two studies focus on different reactions, they share a common goal: using chiral catalysts to precisely control both the reaction sites and the three-dimensional structures of molecules. These advances could significantly improve the efficiency of asymmetric synthesis, which is crucial for making pharmaceuticals and other valuable compounds. Ryu noted that these findings open new possibilities for building complex molecular structures more efficiently, with potential applications in drug development and the synthesis of natural products.