Although not well-known to the public, "asymmetric urea" plays a crucial role in the fields of medicine and agriculture. As a key component of anti-tumor agents, herbicides, insecticides, and supramolecular adhesive materials, asymmetric urea exhibits broad and important application potential. Recently, the team of He Lin, a researcher of the Lanzhou Institute of Chemical Physics of the Chinese Academy of Sciences (hereinafter referred to as the Lanzhou Institute of Chemical Physics), cooperated with the team of Lei Aiwen, a professor of Wuhan University, and made important progress in the field of catalytic carbonylation - successfully using carbon monoxide or carbon dioxide instead of highly toxic phosgene to efficiently synthesize nitrogen containing carbonyl compounds asymmetric urea. This research achievement not only brings safer and more environmentally friendly production methods to the chemical industry, but also provides new possibilities for new drug research and development, materials science, and more. The relevant paper was published in Science. Using catalytic carbonylation as a breakthrough point to catalyze reactions, this mysterious process contains enormous energy. In this reaction, the catalyst itself remains unchanged, but it can significantly affect the progress of the reaction, like an invisible "conductor" leading the chemical reaction in the direction expected by people. In 2016, after completing his studies in Germany, He Lin chose to return to China and work at Lanzhou Institute of Chemical Physics. Faced with various research directions, she turned her attention to the relatively obscure but highly promising field of amine oxidative carbonylation with her keen scientific intuition and profound understanding of national needs. The oxidative carbonylation products of amines, nitrogen-containing carbonyl compounds, have shown broad application prospects in various fields such as new materials, pharmaceuticals, and pesticides. However, the traditional preparation method mainly used in industry - phosgene method, not only has a complex and dangerous synthesis process that requires step-by-step steps, but also involves highly toxic phosgene and produces a large amount of corrosive hydrochloric acid. How to find a safer and more efficient synthesis method has become an urgent problem in the scientific research community. In He Lin's view, in order to promote green and sustainable development in this field, it is necessary to explore new synthetic paths. So, she decided to take catalytic carbonylation as a breakthrough point. Although there is relatively little research in this direction internationally, she firmly believes that it is an important direction for future scientific research. By constantly trying new catalysts and optimizing reaction conditions, He Lin strives to find the most efficient and environmentally friendly method for the oxidative carbonylation synthesis of amines. The scientific research path is full of "thorns". Asymmetric urea is a special chemical substance that contains a carbonyl group in its structure, and two different amine molecular fragments are connected on both sides of the carbonyl group. But currently, it is difficult to directly manufacture asymmetric urea in industry because the amines on both sides are different, making it difficult to control accurately. Therefore, the industry has adopted a step-by-step approach, namely the phosgene method. It is understood that the phosgene method first generates highly toxic phosgene by reacting carbon monoxide with chlorine gas, which creates conditions for subsequent reactions; Next, using an amine to react with phosgene to produce isocyanates or acyl chlorides as intermediate products, it is equivalent to "installing" the first amine onto the carbonyl group; Finally, another amine is reacted with this intermediate to successfully "install" the second amine onto the carbonyl group, thereby generating the desired asymmetric urea derivative and completing the entire preparation process. However, this process produces a lot of highly corrosive hydrochloric acid, which poses a threat to equipment and the environment. Therefore, the research team proposed the concept of synchronous amine recognition through multiple perspectives and research summaries. This innovative approach makes the synthesis of asymmetric urea simple and efficient. He Lin said, "We pioneered the use of the synchronous recognition effect mentioned above, using different amines as substrates to selectively generate high-value asymmetric urea in one step through the reaction of generated metal amides and free radicals. In terms of carbonyl sources, we can use either carbon monoxide or carbon dioxide to reconstruct the process of synthesizing nitrogen-containing carbonyl compounds by phosgene method." However, how to ensure that both different amines can accurately "find" their positions and form asymmetric urea in one step reaction has become a major challenge for the research team. We have obtained key evidence that when primary and secondary amines coexist, the cobalt center only activates the single crystal structure of the primary amine. Combined with the evidence revealed by the Lei Aiwen team using fast scanning X-ray absorption fine structure spectroscopy that the secondary amine preferentially generates free radicals through its interaction with the copper center, it is possible to form a key metal acyl species through nucleophilic attack in one step. Then, when the fragment of the latter half of the amine is attached, the free radicals of the amine can be obtained using the metal copper center He Lin introduced that this discovery is like a beam of light in the darkness, illuminating the direction of the team's progress. However, in order to translate this discovery into a practical and feasible synthesis method, extensive experimentation and validation are still required. The team members constantly tried and optimized, finally finding the best catalytic system and reaction conditions. When the first asymmetric urea was successfully synthesized, all team members were boiling. At that moment, all the hard work and dedication turned into endless joy and pride. It is worth mentioning that this innovation not only reduces dependence on toxic raw materials, but also opens up new avenues for the utilization of carbon dioxide, which has important environmental significance. The key to success cannot be separated from cooperation. In August 2023, the research team submitted a pre submission to Science and received a reply from its deputy editor just over two hours after the email was sent: "It seems like this is a fascinating and valuable research result! I encourage you to submit the full text." This recognition from an authoritative journal has greatly inspired the team members. However, the first round of review did not go smoothly - the editors of Science made a decision to reject the manuscript. Faced with this setback, the team members did not give up. They carefully read the review comments and reflected on the shortcomings in their work. In August of this year, the research team submitted the revised paper to Science again. After the second round of review, the paper was successfully accepted and the scientific research results were recognized by international peers. The success of this research cannot be achieved without collaboration He Lin emphasized the close cooperation with the Lei Aiwen team. "We innovatively integrated the semi reaction of nucleophilic carbonylation and free radical conversion to jointly depict the complete reaction process, which laid a solid foundation for discovering the unique reaction window of asymmetric urea." He Lin further introduced that the study also successfully applied the new method developed by the team, achieving the direct synthesis of small molecule drugs, such as synthesizing Caliprazine - a drug used to treat schizophrenia and manic depression. Their method only requires one reaction step to obtain the target product with a high yield of 89%, and the byproduct is only water, significantly simplifying the traditional preparation process. Behind this achievement is the concept of synchronous recognition activation that we proposed He Lin explained that this is a new catalytic carbonylation reaction mode, which brings new opportunities for fields such as drug synthesis. At present, the team is actively promoting the full chain cooperation in the design, synthesis, and lubrication performance testing of high-end polyol ester base oils, hoping to achieve new breakthroughs in this field through joint research and development. In the future, the research team plans to continue to delve into the field of catalytic utilization of carbon monoxide and carbon dioxide, relying on the Low Carbon Catalysis and Carbon Dioxide Key Laboratory of Lanzhou Institute of Chemical Physics, focusing on practical application scenarios, and carrying out original work. They particularly hope to stimulate new research ideas through the linkage of interdisciplinary platforms. (New Society)